Global estimates suggest there are almost 19 million visually impaired children worldwide, the major cause being uncorrected refractive error (RE).
To assess the prevalence of visual impairment (VI) and RE among Sudanese school-aged children.
Eight randomly selected primary schools from 21 districts in South Darfur State of Sudan were involved.
A school-based cross-sectional study of RE and VI in primary schoolchildren from grades 1 to 8 (children aged 6–15 years) was investigated. A Refractive Error Study in Children (RESC) protocol was implemented to determine the prevalence of RE and VI in these school-aged children. Participants were enrolled through stratified multistage cluster sampling of four all-male and four all-female primary schools from South Darfur State of Sudan. Examination procedures followed the RESC protocol, which included visual acuity (VA) measurements, binocular vision assessments, retinoscopy and autorefraction under cycloplegia, as well as examination of the external eye, anterior-segment, media and fundus.
A total of 1775 children were invited to participate in the study and 1678 were examined resulting in a participation rate of 94.5%. The findings indicated that the prevalence of uncorrected, presenting and best-corrected VA of 6/12 or worse was 6.4% (95% confidence interval [CI], 4.9–7.9), 4.4% (95% CI, 2.9–5.9) and 1.2% (95% CI, 0.3–2.7) respectively. RE was the cause of VI in 57% of participants, retinal disorders in 13.1%, amblyopia in 5.6%, corneal opacity in 0.9%, cataract in 3.7%, with the causes of reduced vision undetermined in 10.3% and various other causes contributed 9.3%. External and anterior-segment abnormalities were observed in 10.2% of children. This was mainly allergic conjunctivitis (5.3%) followed by bacterial and viral conjunctivitis (4.2%). The prevalence of myopia (≥|-0.50 D|) in one or both eyes was 6.8% (95% CI, 5.3–8.3), hypermetropia (≥ 2 D) was noted in 1.9% (95% CI, 0.4–3.4) and astigmatism (≥|-0.75 D|) prevailed in 2.5% (95% CI, 1.0–4.0). Prevalence of VI among school-aged children were associated with the children’s age and grade levels (
Uncorrected RE was a major cause of VI among children in the South Darfur State. There is thus a critical need for developing a comprehensive child eye care plan focusing on the reduction of uncorrected RE through collaboration between key stakeholders and government.
Global estimates indicate that there are around 19 million visually impaired children worldwide; of these, 1.4m are blind and 17.5m have low vision with many of them living in Africa.
Sudan is the second largest country in Africa geographically covering an area of about 1.8 million square kilometres, with an estimated population of more than 39m inhabitants.
This was a cross-sectional, school-based study of VI and RE among children from the South Darfur State of Sudan. The research focused on primary schoolchildren in the 6- to 15-year age range. According to the Ministry of Education, the overall number of learners enrolled in primary schools in South Darfur during 2014–2015 was 338 068 school-aged children consisting of 187 270 boys and 150 798 girls, from public and private schools.
Children aged 6–15 years and who are able to provide parental consent and all children attending the school on the examination days were included in the study.
The exclusion criteria included those whose age did not correspond to the defined age group and those unable to provide parental consent.
The study sample was selected through stratified multistage cluster sampling. Assuming a prevalence of RE (P) = 5% and the worst acceptable prevalence (P) = 4%, according to the estimated prevalence of RE in Africa (5%), South Africa (4%)
Each school selected for the study sample was visited by the principal investigator to explain the purpose of the study to the school administration, and schoolchildren were given requests for consent and permission forms for their parents to allow them to participate in the study. Parents were asked to sign the consent letters if they agreed to allow their children to participate in the study; thereafter, such children were invited to take part in the study.
Optometric research assistants with at least 3 years of experience in clinical optometry were recruited to assist with data collection. The research assistants underwent intensive training in the study protocol procedures. The principal investigator explained and demonstrated these methods in five sessions.
A pilot study was conducted outside the main area of study on 100 children not included in the study sample. The data collected were captured and analysed using the Statistical Package for Social Science (SPSS) Version 22. The results indicated that, some children in the vision examination reported that they had a problem in their vision but after detailed assessment of refraction, together with outer eye and inner eye examination, the results revealed that there was no abnormality in their eyes. In others, their vision examination result was normal after examination of refraction, but the outer eye and/or inner eye results demonstrated that they did in fact have eye problems. This was because of a misunderstanding of the vision examination by schoolchildren or some of them did this to get free medication and spectacles. Because the principal investigator indicated in the child’s consent form that any participants, with eye problems, would be provided free spectacles and eye drops, this could have contributed to this anomaly. Therefore, to overcome this problem in the main study, the principal investigator rechecked the VA for each child after examinations to ensure the accuracy of the measurement of VA.
Ethical permission for conducting the study was obtained from the University of KwaZulu-Natal’s Biomedical Research Ethics committee (ref: BE247/14) and the National Research Ethics Review Committee in Sudan. Permission was also obtained from the South Darfur authorities in Sudan to undertake the research at their facilities. Informed consent was obtained from all participants included in the sample study to facilitate a better understanding of conditions of involvement in the study. The research was conducted in accordance with the Declaration of Helsinki.
Examination procedures employed a modified RESC protocol. Distance VA was assessed using Snellen Tumbling E-chart with E’s of standard size at a 6-meter distance. Children with VA ≤ 6/12 were tested by pinhole and if their VA improved, they underwent cycloplegic refractions. All the schoolchildren underwent a penlight and low-power hand magnifier examination to rule out any anterior-segment abnormalities in the following parts of the eye: eyelids, conjunctiva, cornea, the pupil and pupillary reflex reaction. A cover test was conducted for phorias or tropias and deviations were measured using the corneal light reflex (Hirschberg test) and the Prism Cover Test at distance and near fixation, respectively. The learners underwent motility tests to assess eye muscle function. Subjective refractions were performed by achieving best-corrected VA; while cycloplegic refractions were done for the learners where vision improved with pinhole. First one drop of ophthalmic topical anaesthetic was instilled in each eye, followed by a waiting period of 2 min to achieve ocular surface anaesthesia. Thereafter, children received two drops of 1% cyclopentolate administrated 5 min apart to each eye. If cycloplegia was not completed, then a third drop was administered as required. Cycloplegia was considered to be completed if the pupil dilated to 6 mm or greater and light reflex was absent. After cycloplegia, optometrists refracted learners, regardless of VA: using a Hand Held Auto Refractor/Keratometer (Retinomax K-plus 3). The children with VA ≤ 6/12 whose vision did not improve by pinhole test had ocular and fundus examination by direct ophthalmoscopy and any abnormal findings were recorded. Learners presenting with eye organic defects were referred for further treatment (
Chart illustrating the procedures for assessing vision and detecting vision impairment.
Data forms were reviewed for accuracy and completeness before data capture. The data entry was performed by the principal investigator using SPSS (Version 22), the data were checked for data entry errors and/or missing values before data analysis. The data for each subject were analysed descriptively using standard deviations, modes and percentages. The relationship between measures was determined using correlation, cross-tabulations and chi-squared analysis. The analysis of variance (ANOVA) was used for statistical comparison of means. For all statistical determinations, significance levels were established at
Of the 1775 school-aged children selected to participate in the study, 1678 children presented at schools on the examination days resulting in a participation rate of 94.5%. The records of 12 students who were actually older than 15 years were eventually excluded from the study; thus, the results of 1666 children were analysed as discussed below.
The age of the children ranged from 6 to 15 years with mean age of 10.8 ± 2.8 years (s.d.) while the median age was 11.00 years and modal age was 14 years. There were 839 female children representing 50.4% and 827 male children representing 49.6% of the sample. The mean ages and standard deviations of female and male children were 11.00 ± 2.7 years (s.d.) and 11.00 ± 2.9 years (s.d.), respectively. The age groups most represented were 14 and 12 years at 12.4% and 11.5%, respectively. The groups least represented were 6 years at 5.6%. The differences between the mean ages of male and female children was significant (ANOVA:
A total of 1137 (68.2%) of respondents did not complain of any ocular symptoms. In all, 180 (10.8%) complained of blurred vision, followed by 125 (7.5%) who had itching, 92 (5.5%) who had photophobia and pain, 69 (4.1%) had discharge and redness, 40 (2.4%) complained of foreign body sensation and tearing, 19 (1.1%) complained of headaches, while only 4 (0.2%) complained of difficulty seeing at night.
A total of 1467 (88.1% [95% confidence interval {CI}, 86.6–89.6]) children presented with normal VA (6/6) in the right eye and 1465 (87.9% [95% CI, 86.4–89.4]) children had normal VA in the left eye with 1491 (89.5% [95% CI, 88.0–91.0]) children having normal VA in the better eye. A total of 109 (6.5% [95% CI, 5.0–8.0]), 109 (6.5% [95% CI, 5.0–8.0]), and 101 (6.1% [95% CI, 4.6–7.6]) children had uncorrected VA of (6/9) in the right, left, and better eye, respectively. About 90 children (5.4% [95% CI, 3.9–6.9]) had uncorrected VA ≤ 6/12 in the right eye and 92 (5.5% [95% CI, 4.0–7.0]) in the left eye. Uncorrected VA ≤ 6/12 in one or both eyes was found in 107 children (6.4% [95% CI, 4.9–7.9]), while 74 (4.4% [95% CI, 2.9–5.9]) children had uncorrected VA ≤ 6/12 in the better eye. With best-corrected vision, this decreased to 20 (1.2% [95% CI, 0.3–2.7]) children as shown in (
Distribution of uncorrected visual acuity for right, left and better eye and best-corrected visual acuity by percentage and confidence interval.
UVA | Right eye |
Left eye |
Better eye |
Best-corrected VA |
||||
---|---|---|---|---|---|---|---|---|
% (95% CI) | % (95% CI) | % (95% CI) | % (95% CI) | |||||
6/6 | 1467 | 88.1 (86.6–89.6) | 1465 | 87.9 (86.4–89.4) | 1491 | 89.5 (88–91) | 1640 | 98.4 (96.9–99.9) |
6/9 | 109 | 6.5 (5.0–8.0) | 109 | 6.5 (5.0–8.0) | 101 | 6.1 (4.6–7.6) | 6 | 0.4 (1.1–1.9) |
6/12 | 46 | 2.8 (1.3–4.3) | 50 | 3.0 (1.5–4.5) | 42 | 2.5 (1–4.0) | 4 | 0.2 (1.3–1.7) |
6/18 | 14 | 0.8 (0.7–2.3) | 15 | 0.9 (0.6–2.4) | 11 | 0.7 (0.8–2.2) | 6 | 0.4 (1.1–1.9) |
6/24 | 9 | 0.5 (1.0–2.0) | 9 | 0.5 (1.0–2.0) | 8 | 0.5 (1.0–2.0) | 3 | 0.2 (1.3–1.7) |
6/36 | 7 | 0.4 (1.1–1.9) | 8 | 0.5 (1.0–2.0) | 6 | 0.4 (1.1–1.9) | 4 | 0.2 (1.3–1.7) |
6/60 | 5 | 0.3 (1.2–1.8) | 5 | 0.3 (1.2–1.8) | 4 | 0.2 (1.3–1.7) | 1 | 0.1 (1.4–1.6) |
CF | 5 | 0.3 (1.2–1.8) | 4 | 0.2 (1.3–1.7) | 2 | 0.1 (1.4–1.6) | 1 | 0.1 (1.4–1.6) |
HM |
4 |
0.2 (1.3–1.7) |
1 |
0.1 (1.4–1.6) |
1 |
0.1 (1.4–1.6) |
1 |
0.1 (1.4–1.6) |
UVA, uncorrected visual acuity; CI, confidence interval; VA, visual acuity; CF, count fingers; HM, hand movement.
The findings of VI among 1666 school-aged children are shown in
Prevalence of visual impairment among school-aged children by age groups, gender and school grade.
Category | Children without visual impairment |
Children with visual impairment |
Total | ||
---|---|---|---|---|---|
% (95% CI) | % (95% CI) | ||||
6–7 | 256 | 97 (95.5–98.5) | 8 | 3.0 (1.5–4.5) | 264 |
8–9 | 325 | 97.9 (96.4–99.4) | 7 | 2.1 (0.6–3.6) | 332 |
10–11 | 308 | 94.8 (93.3–96.3) | 17 | 5.2 (3.7–6.7) | 325 |
12–13 | 334 | 93.6 (92.1–95.1) | 23 | 6.4 (4.9–7.9) | 357 |
14–15 | 369 | 95.1 (93.6–96.6) | 19 | 4.9 (3.4–6.4) | 388 |
Male | 787 | 95.2 (93.7–96.7) | 40 | 4.8 (3.3-6.3) | 827 |
Female | 805 | 95.9 (94.4–97.4) | 34 | 4.1 (2.6–5.6) | 839 |
1 | 234 | 96.7 (95.2–98.2) | 8 | 3.3 (1.8–4.8) | 242 |
2 | 225 | 98.7 (97.2–100.2) | 3 | 1.3 (0.2–2.8) | 228 |
3 | 187 | 94.4 (92.9–95.9) | 11 | 5.6 (4.1–7.1) | 198 |
4 | 184 | 93.9 (92.4–95.4) | 12 | 6.1 (4.6–7.6) | 196 |
5 | 208 | 94.5 (93.0–96.0) | 12 | 5.5 (4.0–7.0) | 220 |
6 | 164 | 92.1 (90.6–93.6) | 14 | 7.9 (6.4–9.4) | 178 |
7 | 196 | 95.6 (94.1–97.1) | 9 | 4.4 (2.9–5.9) | 205 |
8 |
194 |
97.5 (96.0–99.0) |
5 |
2.5 (1.0–4.0) |
199 |
CI, confidence interval.
Heterotropia or heterophoria were found in 852 (51.1%) children at the 50-cm fixation distance and in 95 children (5.7%) at the 6-m fixation distance. Most of the children had exophoria at near 781 (46.9%). Tropia was observed in five (0.30%) children; three children had esotropia and two had exotropia.
A total of 1496 (89.8% [95% CI, 88.3–91.3]) children had no abnormalities detected, followed by 89 (5.3% [95% CI, 3.8–6.8]) children who had allergic conjunctivitis. Other eye conditions were conjunctivitis (bacterial and viral), cataract and corneal opacity at 70 (4.2% [95% CI, 2.7–5.7]), 4 (0.24% [95% CI, 1.26–1.74]) and 1 (0.06% [95% CI, 1.44–1.56]), respectively (
Distribution of normal and external eye disease by percentage and confidence interval.
Eye conditions | % (95% CI) | |
---|---|---|
Normal | 1496 | 89.8 (88.3–91.3) |
Allergic conjunctivitis | 89 | 5.3 (3.8–6.8) |
Conjunctivitis | 70 | 4.2 (2.7–5.7) |
Other | 6 | 0.40 (1.1–1.9) |
Cataract | 4 | 0.24 (1.26–1.74) |
Corneal opacity |
1 |
0.06 (1.44–1.56) |
CI, confidence interval.
The prevalence of RE was estimated based on presenting VA (UVA of 6/9 or worse in one or both eyes). Myopia was defined as the spherical equivalent of at least |-0.5 D|, hypermetropia as 2 D or more and astigmatism as |-0.75 D| or more. The RE in one or both eyes was evaluated based on cycloplegic autorefraction. The results of the prevalence of RE in one or both eyes are presented in
The prevalence of refractive error in one or both eyes by age, gender and school grade.
Category | Total children examined | Myopia (95% CI, 5.3–8.3) |
Hypermetropia (95% CI, 0.4–3.4) |
Astigmatism (95% CI, 1.0–4.0) |
Total children needing correction (95% CI, 9.7–12.7) |
||||
---|---|---|---|---|---|---|---|---|---|
% | % | % | % | ||||||
6 | 94 | 9 | 9.6 | 1 | 1.1 | 3 | 3.2 | 13 | 13.8 |
7 | 170 | 5 | 2.9 | 3 | 1.8 | 2 | 1.2 | 10 | 5.9 |
8 | 172 | 7 | 4.1 | 1 | 0.6 | 4 | 2.3 | 12 | 7.0 |
9 | 160 | 10 | 6.2 | 3 | 1.9 | 4 | 2.5 | 17 | 10.6 |
10 | 164 | 6 | 3.7 | 1 | 0.6 | 7 | 4.3 | 14 | 8.5 |
11 | 161 | 13 | 8.1 | 3 | 1.9 | 2 | 1.2 | 18 | 11.2 |
12 | 191 | 13 | 6.8 | 4 | 2.1 | 6 | 3.1 | 23 | 12.0 |
13 | 166 | 12 | 7.2 | 7 | 4.2 | 3 | 1.8 | 22 | 13.3 |
14 | 207 | 23 | 11.1 | 3 | 1.4 | 4 | 1.9 | 30 | 14.5 |
15 | 181 | 16 | 8.8 | 5 | 2.8 | 7 | 3.9 | 28 | 15.5 |
Male | 827 | 57 | 6.9 | 15 | 1.8 | 16 | 1.9 | 88 | 10.6 |
Female | 839 | 57 | 6.8 | 16 | 1.9 | 26 | 3.1 | 99 | 11.8 |
1 | 242 | 13 | 5.4 | 4 | 1.7 | 5 | 2.1 | 22 | 9.1 |
2 | 228 | 9 | 3.9 | 3 | 1.3 | 3 | 1.3 | 15 | 6.6 |
3 | 198 | 11 | 5.6 | 3 | 1.5 | 8 | 4.0 | 22 | 11.1 |
4 | 196 | 18 | 9.2 | 1 | 0.5 | 2 | 1.0 | 21 | 10.7 |
5 | 220 | 12 | 5.5 | 2 | 0.9 | 3 | 1.4 | 17 | 7.7 |
6 | 178 | 24 | 13.5 | 10 | 5.6 | 8 | 4.5 | 42 | 23.6 |
7 | 205 | 15 | 7.3 | 2 | 1.0 | 6 | 2.9 | 23 | 11.2 |
8 |
199 |
12 |
6.0 |
6 |
3.0 |
7 |
3.5 |
25 |
12.7 |
CI, confidence interval.
Myopia, hypermetropia and astigmatism were prevalent in 114 (6.8% [95% CI, 5.3–8.3]), 31 (1.9% [95% CI, 0.4–3.4]) and 42 (2.5% [95% CI, 1.0–4.0]) children, respectively. The prevalence of myopia was more common in 15–year-old children (23; 11.1% [95% CI, 9.6–12.6]) than in young children aged 7, 8, 9 and 10 years wherein the prevalence was 2.9%, 4.1%, 6.2% and 3.7%, respectively. Myopic prevalence was not significantly different between male (6.9% [95% CI, 5.4–8.4]) and female (6.8% [95% CI, 5.3–8.3]) children. Similarly, the prevalence of hypermetropia among male and female children was not significantly different at 1.8% (95% CI, 0.3–3.3) and 1.9% (95% CI, 0.4–3.4) respectively. The prevalence of astigmatism was more common among females at 26 (3.1% [95% CI, 1.6–4.6]) than males at 16 (1.9% [95% CI, 0.4–3.4]). Moreover, the prevalence of hypermetropia was higher among 13 year olds (4.2%) followed by 15 year olds (2.8%) and lower for the ages 10, 8, and 6 years, which was 0.6%, 0.6% and 1.1%, respectively. The prevalence of myopia compared with emmetropia was statistical significant (
The prevalence of the children who needed refractive correction in one or both eyes was 187 (11.2%) but no child presented with spectacles. The need for spectacles was the highest for both genders in the higher-grade levels.
Posterior-segment examination revealed that a total of 1631 (97.9% [95% CI, 96.4–99.4]) children had no abnormalities. Media and fundus abnormalities were observed in 35 (2.1%) children. Retinal disorders occurred in 17 (1.0% [95% CI, 0.5–2.5]) children. Vitreous abnormalities were present in 4 (0.2% [95% CI, 1.3–1.7]) children and the causes of reduced vision were undetermined in 14 (0.8% [95% CI, 0.7–2.3]) children.
The causes of UVA of 6/12 or worse at least in one eye are presented in
Causes of uncorrected visual acuity 6/12 or worse.
Causes | Eye with uncorrected VA 6/12 or worse |
Children with VA 6/12 or worse in one or both eyes |
Prevalence in the population one or both eyes, % (95% confidence interval) | ||||
---|---|---|---|---|---|---|---|
Right eye |
Left eye |
||||||
% | % | % | |||||
Refractive error | 52 | 55.9 | 56 | 57.7 | 61 | 57.0 | 3.7 (2.2–5.2) |
Amblyopia | 5 | 5.4 | 5 | 5.2 | 6 | 5.6 | 0.4 (1.1–1.9) |
Corneal opacity/scar | 0 | 0.0 | 1 | 1.0 | 1 | 0.9 | 0.1 (1.4–1.6) |
Cataract | 4 | 4.3 | 2 | 2.1 | 4 | 3.7 | 0.2 (1.3–1.7) |
Retinal disorder | 14 | 15.1 | 13 | 13.4 | 14 | 13.1 | 0.8 (0.7–2.3) |
Undetermined cause | 11 | 11.8 | 11 | 11.3 | 11 | 10.3 | 0.7 (0.8–2.2) |
Other cause | 7 | 7.5 | 9 | 9.3 | 10 | 9.3 | 0.6 (0.9–2.1) |
Any cause | 93 | 100 | 97 | 100 | 107 | 100 | 6.5 (5.0–8.0) |
About 1410 (84.6%) school-aged children had normal vision and no ocular abnormalities and were not referred. The distributions of the remaining schoolchildren who received eye care or who were referred for further treatment were as follows: 216 (13.0%) schoolchildren had uncorrected RE, inflammatory and allergic eye conditions. The learners with uncorrected RE were given spectacles and the others were provided with eye drops. Forty (2.4%) learners presented with other eye diseases and were referred to an eye hospital for further treatment.
Cycloplegic refractions were used to assess the RE of schoolchildren in this study as for previous studies by Naidoo et al.
The prevalence of RE in either eye was 178 (11.2%), which is lower than that found by school-based studies conducted in similar age groups such as those by Paudel et al.
The prevalence of RE among schoolchildren in this report was 11.2%, which is statistically significant for age and grade levels of the children (
The prevalence of myopia (spherical equivalent RE of −0.5 D or more in one or both eyes) was found in this study to be 6.8%, which was similar to that of 6.8%
The prevalence of hypermetropia in this study of 1.9% was significantly lower than that reported in other studies of similar school-aged children conducted in other countries; for instance, 26.4%
The prevalence of astigmatism in the current study was 2.5%. This is much lower than the findings by Ogbomo and Assien among Ghanaian children at 6.6%
In this study, uncorrected RE was the most common cause of VI among school-aged children, which accounted for 57% of cases. This result is similar to that found in many studies, which used the RESC protocol in African school-aged children such as in South Africa (66.4%
This study revealed that the prevalence of myopia in school-aged children was slightly higher than that found in previous studies conducted among African school-aged children. However, the present study agrees with recent studies that there is a gradual increase in myopia over the last decade and this might be because of increased time spent indoors and lack of time outdoors as children are increasingly engaging in tasks using technology such as computers and mobile phones rather than outdoor activities. This trend of increasing myopia has been stated by Holden et al.,
The current study had some limitations. Firstly, not all the schools in the South Darfur State were included in the sampling frame and the schools in the camp of internally displaced people were not included in this study. Thus, our findings reflect only the prevalence of VI and RE among school-aged children studying at public and private schools in the South Darfur State. Secondly, we conducted all the clinical eye examinations in the schools to improve the participation rate. However, conditions such as illumination, ventilation and comfort were different from school to school. However, we did ensure that we chose similar environments to conduct the study. Thirdly, the number of schoolchildren decreased in higher-grade levels, which may introduce bias in the results of VI and RE, as the numbers were not uniform across all school grades. Finally, our study employed a modified RESC protocol. This involved minor changes in the instruments that were used for collecting the data as recommended by the original protocol. We used Snellen (Tumbling E-optotype), torch and magnifier as opposed to LogMAR charts and slit lamp as well as ophthalmoscopy as opposed to fundus biomicroscopy.
To our knowledge, no similar study has been conducted in this region; thus, the data obtained makes a valuable contribution to the understanding of eye health challenges in the South Darfur State of Sudan. The study concluded that uncorrected RE was a major cause of VI among school-aged children in this region. These findings indicate an urgent need for developing a comprehensive childhood eye care plan for delivering eye care services to school-aged children, through collaboration between government, private sectors, stakeholders and non-government organisations working in preventing avoidable childhood blindness and VI. This supports the need for regular vision screening programmes for the prevention of avoidable causes of vision.
The African Vision Research Institute (AVRI) funded this study and we are grateful for the support of the Brien Holden Vision Institute. We thank Professor Kamal Hashim Binnawi, coordinator for prevention of blindness in Sudan, for his support and the school health promotion managers in South Darfur State Dr Jamal and Dr Adam Mousa. We also thank the data collection team for their hard work and all the students who participated in the study.
The authors declare that they have no financial or personal relationships, which may have inappropriately influenced them in writing this article.
S.H.A. was the project leader who was responsible for the experimental and project design under the supervision of P.C.C-F. and K.S.N. S.H.A. conducted all clinical research. P.C.C-F. and K.S.N. made conceptual contributions and provided guidance for the study. S.H.A. was responsible for the writing of this article with input and edits from P.C.C-F. and K.S.N.