V.
CLINICAL
EXPERIENCE
1. Phase 1: Training and preliminary observations
During June and July 2013, I assisted Dr.Francesca Colombini, a Pediatric Neuropsicomotricity Technician of the 0-2 Neurology Section of Stella Maris Institute in Pisa, in the visual acuity assessment of patients in our surgeries. The goal of the training was to become familiar with the items of the Teller Acuity Cards, and to observe infants’ visual responses correctly.
In a 6-month old baby, we administered both the Teller Cards and the EyePad acuity tests, and we verified together the interpretability of the tactile vibration feedback of the instrument and the best environment brightness conditions to administer the test. After this preliminary trial, Zanchettin and Mazziotti modified the application to obtain the actual vibration feedback, taking into account the observations noted during this training period.
2. Phase 2: Experimental design
I defined two main purposes: the first one is to compare the acuity values, assessed with the
EyePad, with the normative data obtained with the Teller Acuity Cards and described in
literature; the second one is to assess the reliability of the tool performing a second test, on the same subject, after 24 hours.
To obtain a behavioural visual response, it is important that the baby is in an optimal state, which is a necessary condition to keep attention and collaboration. This factor may influence the test result, so I introduced the variable ‘compliance’ in order to evaluate the results without this potential confounding factor. The compliance value, assigned at the end of each assessment, can be high (H), medium (M) or low (L) and it is based on a global clinical impression. The factors which may influence the compliance are: the need to interrupt the test session because of sleepiness, crying, generic discomfort of the baby, distractions from the environment, or a test duration longer than ten minutes.
3. Phase 3: Selection of the patients
Infants were recruited from the Neonatology Unit in S. Chiara Hospital of Pisa from July the 27th to August the 30th, 2013. According to the criteria adopted by Ricci’s group [74], I selected all babies who were born between 37w and 41w of gestational age, by a spontaneous delivery or by an elective pre-labor-cesarean section that was not made for fetal causes. Exclusion criteria were: emergency cesarean section; Apgar score <7 at 5’; evidence of respiratory distress; birth
weight <10° or >90° centile; SGA fetus; jaundice requiring photo-therapy at the time of the assessment; history of fetus or maternal infections; prolonged rupture of membrane or abnormal meconial fluid; psychiatric drug use during pregnancy; familiar history of epilepsy or neurological diseases. The global clinical judgment of Dr. Cristina Tuoni and Dr. Erika Fiorentini of the Neonatology Unit, was also taken in account in the patient selection.
Written consent to the procedure was obtained, in the first day after birth, from thirty-one mothers of the babies who met inclusion criteria.
4. Phase 4: Data collection
Infants were assessed on the second (around 24h) and on the third day (around 48h) of life, before discharge. The mean age in hours at time of the first test was 28h (range 17-39 hours); at the re-test time the mean age in hours was 52h (range 43-62 hours). Twenty-nine newborns performed the 24h test; twenty-five newborns carried out the 48h test; twenty infants completed the experimental protocol with both test and re-test. Three infants were not able to complete any test since they were asleep or not in an adequate behavioural state during the time interval when I was in the nursery for the assessments.
Population clinical characteristics are resumed in Table 1.
The evaluation was performed between feeds, in a spontaneous awake status, during the afternoon after all clinical routine examination had already been performed, and the environment was quiet enough.
The babies were posed on a horseshoe pillow to maintain them in a controlled supine position, without coarse movements of the limbs, with the body inclined by 30°. Tests were performed in an area where any light disturbance from windows or neon-lamps could be reflected by the tablet screen, in accordance with the training phase conclusions.
Patient Parental
Consent Birth Date Birth Hour
Gestational
Age. Birth Weight
ggmmNF X gg/mm 24:00 h ** w + *d **** gr 2907GS X 29-jul 40 3354 3007AR X 29-jul 09:14 38+3 2980 3007SC X 29-jul 23.:00 41+3 3880 3107TL X 29-jul 01:30 40+2 3796 3107LC X 29-jul 01:53 38 3500 0108GT X 31-jul 17:27 39+3 3476 0108DC X 31-jul 11:25 39 3216 0108RdS X 31-jul 22:20 38+4 2850 0508MV X 04-aug 19:03 40+6 3150 0708GG X 06-aug 08:50 38+1 3280 0708ED X 06-aug 11:10 37+4 2980 0708GC X 06-aug 13:34 40+3 4130 0808MB X 07-aug 06:51 40+3 3494 0908CC X 08-aug 07:14 41+2 3444 1308EQ X 12-aug 04:11 38 3222 1308DO X 12-aug 16:47 37 3530 1408BS X 13-aug 09:37 41+2 3794 1408NT X 13-aug 15:12 38+5 3416 1408VP X 13-aug 15:38 38 3248 1408AB X 13-aug 11:59 39+4 3416 2008AF X 19-aug 04:35 40 3864 2008MdP X 19-aug 09:46 39 3240 2008LB X 19-aug 00:42 40+2 3074 2008FG X 19-aug 21:51 31+1 3316 2108MR X 20-aug 07:40 39+4 3166 2108GB X 20-aug 09:47 39 3420 2108AC X 20-aug 19:40 38+6 3436 2108DL X 20-aug 17:30 37+6 2534 2108GL X 20-aug 17:20 37+6 2544 2208VS X 21-aug 04:11 40 3380 2308ZG X 22-aug 08:45 40+2 3820 2308VC X 22-aug 09:45 38+5 3240
Table1: Clinical characteristics of the experimental population; each patient has a univocal
5. Phase 5: Data Analysis
Acuity values of the 24hours-tests are resumed in Table 2.
The mean Acuity value of the twenty-nine 24h-tests is 1.13 cyc/deg with a standard deviation of 0.41 cyc/deg. The distribution of the data are represented in Figure 2.
To demonstrate the coherence between these results and the data in literature, I performed a comparing t-test using, as reference, the paper by Fazzi et al. “Visual acuity in the first two years of life
in healthy term newborns: an experience with the Teller acuity cards”, which also
reviews previous visual acuity studies [27].
Fazzi’s review reports mean acuity values, of term-newborns within the first week of life, obtained by: Yamamoto et al. - 0.7 cyc/deg with a SD of 0.5 octaves [75];
by Dobson et al. - 1 cyc/deg with a SD of 0.6 octaves [76];
by Vital-Durand et al. - 1,5 cyc/deg, SD is not reported [77];
by Fazzi et al. corresponding to - 1,4 cyc/deg with a SD of 0.6 octaves [73]. Patient Age (hours) Acuity (cyc/deg) Compliance Test 48h 0108DC 30:05 0,19 M Y 2008MdP 29:32 0,62 H N 2108GL 24:12 0,62 M N 2108GB 31:33 0,63 M N 1408NT 24:20 0,69 L Y 2008AF 37:25 0,71 M Y 0708ED 27:40 0,8 M N 2308ZG 30:20 0,89 H Y 0908CC 31:13 0,92 H Y 1408AB 29:55 0,93 M Y 3007SC 16:50 0,98 H Y 2108MR 30:56 0,99 H Y 1408BS 29:01 1 H N 0708GG 33:03 1,04 M Y 2308VC 29:12 1,06 H Y 2008LB 39:08 1,18 H Y 2108DL 24:18 1,21 M Y 2008FG 19:42 1,23 H Y 0508MV 22:15 1,36 M Y 1308EQ 37:22 1,41 M Y 2208VS 34:41 1,41 H Y 3007TL 40:08 1,44 H N 0108GT 21:33 1,44 H Y 1408VP 22:55 1,49 H Y 2907GS 22:42 1,56 L Y 0108RdS 19:25 1,61 H Y 2108AC 22:19 1,72 M Y 1308DO 24:32 1,76 H Y 0808MB 32:57 1,87 M Y 3007AR 30:31 x vL N 3107LC 37:07 x vL N 0708GC 28:41 x vL N
Table2: Static Acuity assessment results at the 24h test.
The fourth column indicates compliance values. The last column indicates if the infant completed (Y) or not (N) the re-test at 48h of life.
Fig.2: Static Acuity assessment results at the 24h test.
Mean Acuity value of the twenty nine 24h tests is 1.13 cyc/deg (vertical tracts-line); standard deviations are represented by the pointed-lines. The black line is a representation of the distribution of the 24h acuity test results. It is important to note that the EyePad gives back an acuity value which is a number, derived on the psychometric function, along a continuous numerical scale of frequencies, in cyc/deg. In this manner, in our analysis, the standard deviations and the analysis of the distribution are calculated in a linear way.
But results by previous works, which we have to refer to, were obtained by testing the specific gratings contained in each Teller Acuity Card. The obtained acuity values are related only to specific points of the scale of the frequencies, and not to a continuous psychometric function. The difference between a point (card) and the next one was ½ octave and standard deviations, in this works, were expressed in octaves, an exponential scale.
To compare data, it is necessary to transform the octave-ranges in linear intervals of values. The minimum value of the harmonics composing the octave scale, is usually the smaller frequency contained in Teller Acuity Cards, which is 0.32 cyc/deg (F). The scales usually adopted in literature have ½ octave steps between points. To obtain the value x, expressed in cyc/deg, of the “oct” value of a range of acuities, we can apply this transformation:
x = F * ( 1.5 )oct
Subsequently, I grouped the results obtained by works which refer to populations of healthy term newborns, reviewed in the Fazzi’s paper, obtaining the mean of the acuity values and the mean of the SDs by all these works. I expressed the SD in a linear way applying the
0 0,05 0,1 0,15 0,2 0,25 0,3 0,35 0,4 0 0,2 0,4 0,6 0,8 1 1,2 0,00 0,50 1,00 1,50 2,00 2,50 3,00 S u b je ct s f ra ct io n 24h Acuity (cyc/deg) Serie1 Mean Distribution Analysis -DS +DS
transformation of the equation above, and obtained a mean of 0.998 cyc/deg with a SD of 0.403cyc/deg
A graphical comparison of the distributions of literature data and our data is represented in Figure 3.
It is worth to observe that both means are comprised within 1SD of the other dataset.
Fig.3: Static Acuity assessment results at the 24h test distribution (black line), compared with the mean acuity results
obtained by Fazzi’s review (gray line) 0.998 cyc/deg. Complete vertical lines represents the mean values of the distributions. Vertical dashed lines represent the 1SD of distributions.
0 0,2 0,4 0,6 0,8 1 1,2 0,000 0,500 1,000 1,500 2,000 2,500 3,000 S u b je ct s
Acuity values (cyc/deg)
Our 24h acuity distribution Litterature Acuity distribution
I assumed the whole literature data set contains at least one hundred observations, and performed a t-test to compare it with our data collection.
Our Dataset Literature Data set MEAN ACUITY (cyc/deg) 1,13 0,998
SD (cyc/deg) 0,41 0,403
N^.OF OSSERVATIONS 29 100
We obtain a t-value of 1.54. With a significance level of 95% the p-value is 0.13 and we observe that our p is p>0.05. So there is no statistical difference between acuity results obtained by the
EyePad and the mean acuity values obtained by Teller Acuity Cards from a population of healthy
term-born children within the first days of life.
In order to obtain a stronger correlation between the EyePad performance and the Teller Acuity Cards, it will be necessary to perform further trials with both examinations on the same subject. This analysis describes the external validity of the tool and demonstrates its accuracy.
To illustrate the internal validity of the tool, I analyzed data from test-retest acuity values obtained from the twenty subjects who completed the experimental protocol (Table 3).
Compliance 24h-Test 24-Test cyc/deg Compliance 48h-Test 48h-Test cyc/deg 24/48 Compliance Diff. TRtD H 0,98 H 1,41 0 0,43 H 0,99 H 1,02 0 0,03 H 1,06 H 1,00 0 0,06 H 1,23 H 1,07 0 0,16 H 1,44 H 1,38 0 0,06 H 1,76 H 1,78 0 0,02 M 0,93 M 1,00 0 0,07 H 0,89 M 1,25 1 0,36 H 1,49 M 1,07 1 0,42 L 1,56 M 2,01 1 0,45 M 0,99 H 1,78 1 1,59 M 0,71 H 1,76 1 1,05 M 1,04 H 1,70 1 0,66 M 1,21 H 1,57 1 0,36 M 1,41 H 1,39 1 0,02 M 1,72 H 1,68 1 0,04 M 1,87 H 1,10 1 0,77 M 1,36 L 0,80 1 0,56 H 0,92 L 1,08 2 0,16 H 1,18 L 0,65 2 0,53 H 1,41 L 0,61 2 0,80 H 1,61 L 0,68 2 0,93 L 0,69 H 1,36 2 0,67
Table3: Test and re-test data. The “24/48 Compliance Difference” column displays
homogenous groups of level of compliance between the first and the second examination: “0” indicates the same compliance in both assessments (for example H-H); “1” indicate a one-step size difference (for example L-M); “2” indicates a two-step size difference (L-H), TRtD: Test-retest Difference between acuity values in the 24h and 48h test.
A variation in the compliance of the newborn during the assessments could bias the interpretation of the differences between the first and the second examination. Therefore, I separated the achieved results in three homogeneous groups, based on the compliance status in both test and re-test examinations. Then, I compared the two series of data for each group calculating the mean test/re-test difference, and the Pearson coefficient. This derived value describes the correlation between two series of numbers: if it is > 0, the series x and y are directly
These comparisons are represented in the following tables (4-7).
0,44 Mean test/retest difference (TRtD) 0,12 Mean TRtD same compliance 0,57 Mean TRtD one-step compliance diff. 0,62 Mean TRtD two-steps compliance diff.
Table4: Test and re-test difference comparison.
As observed in Table 5, when the EyePad acuity test is administered in the same compliance condition, the reliability of results is high (Pearson value 0.80) and the tool can reproduce the detection of the same subject’s acuity. The positive relation between this series is represented in Figure 4. 0,98 SAME COMPLIANCE 24 e 48 1,41 0,99 1,02 1,06 1,00 1,23 1,07 1,44 1,38 1,76 1,78 0,93 1,00 Pearson 0,80
Table5: Test and re-test values in the babies with the same
compliance level at time of the first and the second examination.
Fig.4: Relation between acuity results when compliance is in complete agreement in both assessments. The regression
which represents the relationship between data is close to an y=x line (y=1.02x).
y = 1,0193x 0,00 0,20 0,40 0,60 0,80 1,00 1,20 1,40 1,60 1,80 2,00 0,00 0,50 1,00 1,50 2,00 A cu it y 4 8 h Auity 24h
Complete compiance agreement
Complete compiance agreement
When the collaboration of the subjects varies between the assessments, data results are not in agreement, demonstrating that the collaboration of the infant is a factor which influences the execution of a behavioural test strongly.
This is confirmed by the poor correlation between the two series of data (Pearson < 0) as shown in Table 6 and Table 7, and illustrated with the negative regression in Figure 5.
0,89 COMPLIANCE DIFFERENCE1 1,25 1,49 1,07 1,56 2,01 0,19 1,78 0,71 1,76 1,04 1,70 1,21 1,57 1,41 1,39 1,72 1,68 1,87 1,10 1,36 0,80 Pearson -0,33
Table6: Test and re-test values in the babies with a one-step
compliance level difference at time of the first and the second examination. 0,92 COMPLIANCE DIFFERENCE2 1,08 1,18 0,65 1,41 0,61 1,61 0,68 0,69 1,36 Pearson -0,89
Table7: Test and re-test values in the babies with a
two-steps compliance level difference at time of the first and the second examination.
Fig.5: relation between results of the 24h and the 48h test when compliance, during the assessments, was not in
agreement. The inclination of the line (-0,31) indicates a poor correlation between the two series of data.
Taking into account this last observation, we can conclude that the tool has the capability to detect differences in acuity performances, an important characteristic when we are interested to a follow-up study of a patient. In other words, this analysis demonstrates the reliability of the EyePad tool in detecting real changes in acuity values.
y = -0,31x + 1,66 0,00 0,20 0,40 0,60 0,80 1,00 1,20 1,40 1,60 1,80 2,00 0,00 0,50 1,00 1,50 2,00 A cu it y 4 8 h Acuity 24h
Different compliance
Different compliance Linear relationship6. Phase 6: Case report
It is necessary to design and perform an extensive data collection to demonstrate the feasibility of the EyePad assessment in a clinical population. However, we tried to apply a visual acuity evaluation with the EyePad in a newborn with neurological damage, due to a perinatal asphyxia, depicted by MRI, and describe here this case report.
Parient-1 was admitted in the S.Chiara Hospital NICU from Pontedera first-line hostpital. Patient-1 was born by an emergency cesarean section performed at 39+6 weeks of gestation, after the detection of marked oligohydramnios and anomalies in the fetal cardiac signal pattern, which warned that a fetal distress was present. Clinical history during pregnancy was referred as normal.
At birth, the baby showed no respiratory and no cardiac activities. Aspiration of meconium from the high airways was performed, followed by ventilation with facial mask and ambu, without recovery of cardiac activity. Then, resuscitation has been undertaken with tracheal intubation, endotracheal administration of epinephrine 0.2mg and heart massage. The cardiac activity has been re-established after 7-8 minutes.
Clinical examination at admission to the NICU revealed: weight of 2270gr; cranial circumference of 33cm; heart rate of 88bpm; respiration rate, with mechanical ventilation, of 66 breaths per minute; no cyanosis was noted but the skin was cold.
Neurological examination revealed: generalized hypotonia; poor spontaneous motor activity; weak pupillary, grasping and absent sucking reflexes.
During the clinical course the baby manifested seizures, which were treated with phenobarbital. According with Sarnat and Sarnat classification, the clinical picture of Patient-1 can be described as a HIE Grade II.
When the clinical condition of Patient-1 was stable, around ten days of life, it was performed a MRI examination. The infant underwent imaging MRI scanner with conventional T1-weighted, T2-weighted and Diffusion sequences. Early imaging is important for defining perinatally acquired lesions.
According with the criteria by Okereafor et al. [78] imaging reveals a picture of brain lesion classifiable as Pattern I.
Basal ganglia and thalami (BGT) appear severely affected: slightly swollen BGT, homogenous in appearance. Signal from myelin in the posterior limb of the internal capsule (PLIC) is markedly reduced. White matter (WM) has large areas of abnormality (black arrows in Figure 6) and loss of gray matter/WM differentiation (see Figures 6-7). Cortical abnormalities included both a loss of markings, as seen with loss
of gray matter/WM
differentiation.
Fig.6: T2-weighted scan of Patient-1 at 10 days of life.
Diffuse abnormal aspect of the white matter, especially in the posterior areas (black arrows) with marked loss of gray matter/WM differentiation (white arrows).
Swollen BGT, homogenous in appearance, with markedly reduced signal from myelin in the PLIC.
The baby was maintained in an incubator, with monitoring of vital functions continuously.
In these conditions, at around fifteen days of life, we performed a Visual Acuity test with the EyePad
Neurological examination at time of the assessment revealed: generalized hypotonia, generalized hypotonia; poor spontaneous motor activity; brisk tendon reflexes with sustained clonus on inferior limbs.
Fig.7: comparison of a T1-weighted scan of a Pattern V brain, in an infant aged 5 days and Pattern I of Patient-1 at
10 days of life.
A) Normal T1-weighted image demonstrating normal T1 hyperintensity of the PLIC (black arrow). No abnormalities in gray matter or WM are shown.
B) BGT show abnormal T1 hypointensity in signal; wide anomalies in WM; diffuse loss of differentiation in the cortical grey matter/WM, also evidenced in calcarine scissure (white arrow).
The baby was in a quiet, awake state and eyes were open spontaneously. Few spontaneous ocular movements were observed, fixation of gaze to an object was possible with a poor, not fluent pursuit. With these characteristics it was possible to observe correctly the behavioural visual responses to the EyePad stimuli.
The assessment has been performed at a distance of around 25cm from the EyePad screen, opening a lateral door of the incubator, with little perturbation of the baby’s environment. The testing session have had a duration of 5’, with a single brief interruption (less than a minute) because of discomfort signs of the baby.
The compliance level assigned was High (H).
Fig.9: The summary screenshot of the EyePad visual acuity Test. The blue line represents the psycometric function;
the green boxes represent the stripe widths showed during the assessment; the red line is the visual acuity value calculated on the function.
The result of this assessment is represented in Figure 9 by the summary screenshot given by the
EyePad. The visual acuity of Patient-1 has a value of 0.63 cyc/deg , which is clearly below the
mean of healthy newborns (1.13 cyc/deg) and lower than the minimum visual acuity registered by infants who showed high compliance during the assessment (0.89 cyc/deg).
This is a single case report, and it doesn’t allow us to draw conclusions about the specificity and the sensibility of the tool. Nevertheless, this experience with a baby with neurological damage demonstrates the feasibility of the EyePad visual examination in critical clinical conditions, such as a baby in care in a NICU.
