Parallelism between hypovitaminosis D3 and recently detected myopia in children with amplified screen use in the COVID-19 era—A preliminary study

Abstract

Purpose:

This introductory study aims to analyze the association of serum vitamin D3 levels with recently detected myopia in Indian children following home confinement post-COVID-19 pandemic.

Methods:

Children aged 5–15 years who had not attended physical school in the past 1 year and visited the ophthalmology department with various ocular symptoms were divided into two groups: the myopic group with recently detected myopia and the non-myopic group with ocular ailments other than myopia. All children underwent basic ophthalmic evaluation and a general physical examination. Blood samples were collected for serum vitamin D3 levels. A pretested questionnaire inquiring about the duration of exposure to a digital screen, outdoor activities, and socioeconomic status was filled out for all children.

Results:

The mean serum vitamin D3 level in the myopic group was 28.17 ± 15.02 ng/dl in comparison to 45.36 ± 17.56 ng/dl in the non-myopic group (P value < 0.05). Linear regression of the data establishes that myopia is associated with hypovitaminosis D3 (OR- 13.12, 95% CI 2.90–50.32, a P value of 0.001). The correlation between spherical equivalent and vitamin D3 levels was significant (Pearson correlation value: 0.661). In the myopic group, 63.3% of children had screen use >6 hours against 43.3% of children in the non-myopic group. In the myopic group, 33.3% of the children had an outdoor activity duration of <2 hours against 6.6% of children in the non-myopic group.

Conclusion:

This study proposes hypovitaminosis D3 as a strong factor associated with the development of myopia in children. Although it is a preliminary study, it suggests that the trial for vitamin D3 supplementation in young children to delay or cease the development of myopia is warranted.

Myopia is a common preventable cause of visual impairment in children and adolescents. The prevalence of myopia has been estimated to be 5.3% in Indian children and 35.6% in adults.[1,2] The incidence of myopia is more in the Asian population as compared to other tropical countries.[3,4] Along with genetic susceptibility, numerous environmental factors like near work, increased screen use, and time spent outdoors are also recognized as conducive factors for the development and progression of myopia.[5-7] A novel factor that has been under a lot of scrutiny by researchers for its association with myopia is the serum vitamin D3 (vit D3) level. Some studies found the serum vit D3 level as a substitute or a marker of time spent outdoors, whereas few suggest it as an independent factor associated with myopia.[8,9] Vit D3 (cholecalciferol) is a fat-soluble vitamin that regulates calcium and phosphorus metabolism with 1,25(OH) 2D (calcitriol) as its active metabolite.[10] Vit D3 is majorly formed in the skin on sunlight exposure and is also obtained from dietary sources. In the Indian population, children have a higher incidence of hypovitaminosis D (84.9% to 100%) as compared to adults.[11]

After the relaxation of the COVID-19 lockdown when normal ophthalmology outpatient operation was resumed in western Maharashtra, we noticed a surge in the frequency of children with recently detected myopia. A review of the literature showed an increase in the progression of myopia, especially in children of the age group 5 to 15 years in the post-COVID-19 era.[12,13] To contain the spread of COVID-19, multiple countries laid down strict lockdowns, and all school teaching and education were delivered online. This increased screen time and restricted outdoor activities due to home confinement, which were suggested as the cause of the progression of myopia. Although few studies[14] have shown progression in myopia during COVID-19 times, there is a scarcity of literature on its association with serum vit D3 levels, especially with recently detected myopia.

With this preliminary study, we have endeavored to analyze the association of hypovitaminosis D3 with recently developed myopia in Indian children following home confinement due to the COVID-19 pandemic.

Methods

This observational study was conducted at the ophthalmology department of a tertiary-care center after approval by the institutional ethics board (IEC/2022/05). Written consent was obtained from the parents of all participants. This study included children of the age group of 5–15 years who had not attended physical school in the past 1 year and visited the ophthalmology department with various ocular symptoms. All children were divided into two groups: the myopic group (case group) included children who were recently detected with myopia and had no previous history of refractive error or glass usage. The non-myopic group (control group) included children who showed no refractive error and were treated for ocular ailments other than myopia like conjunctivitis, allergic pathology, etc., Exclusion criteria included children with diagnosed malnutrition, inborn errors of metabolism, consuming any vit D3 supplementation, and any severe morbidities affecting their growth. A pretested questionnaire was administered by the investigator. The questionnaire inquired about the number of hours spent on screen (computer/smartphone use), duration of outdoor activities throughout the day, eating habits, parental history of myopia, and their socioeconomic status. The modified Kuppuswamy score[15] was used to assess the socioeconomic status of the study population. The modified Kuppuswamy scale divided social strata into five classes from upper class to lower (I to V). In our study, children were either from the upper-middle (middle) or upper-lower (lower) class. All children underwent basic ophthalmic evaluation including visual acuity, cycloplegic refraction, slit-lamp examination, and fundus examination. Visual acuity was measured using the log Minimum angle of resolution (MAR) chart at 6 m in ambient light, and for children who were not able to identify letters, Landolt C or Allen cards were used. The spherical equivalent (SE) refraction of each child was recorded for both eyes, and data from the worst eye were used for analysis. Myopia was defined as an SE of −0.50 D or less. A general physical examination (height, weight, and BMI) was performed for each child. A blood sample was collected from each individual on the day of the ophthalmic examination. The circulating vit D3 level was used to determine vit D3 deficiency or sufficiency and was taken as the common value of vit D3 metabolism (including sun-induced vit D3 and dietary obtained vit D3). The serum vit D3 level was measured using the enzyme immunoassay competition method with final fluorescent detection (ELFA) (Biomerieux: Vidas automated system). A serum vit D3 level of ≥ 30 ng/ml was taken as normal, and any value <30 ng/ml was taken as low or deficient.[16]

Statistical analysis

Data were collected and entered into an Excel spreadsheet for cases (myopic) and controls (non-myopic) by the principal investigator. Double entry of data was cross-checked. The continuous variable was reported as mean + SD and the nominal variable as proportion. An independent t-test was used for the interval scale variable, the and Chi-square test was used for categorical variables. A binary logistic regression model was used to assess the association between case and control groups with predictor variables. Statistical significance analysis was performed using IBM SPSS (version 23). A P value less than 0.05 was regarded as statistically significant.

Results

Our study included 60 children in total (n = 60) classified into the myopic group (n1) and non-myopic group (n2) with 30 children each (n = n1 + n2). In our study 44 (73.3%) males and 16 (26.45) females were included. The mean serum vit D3 value in the myopic group (cases) was 28.17 ± 15.02 ng/dl in comparison to 45.36 ± 17.56 ng/dl in the non-myopic (control) group. Both groups showed a significant difference between levels of vit D3 (P value = 0.001) with 95% CI (−25.6294 to − 8.7372). Overall, 28 children were from the upper-lower (lower) socioeconomic status as per the modified Kuppuswamy scale and 12 children gave a parental history of myopia. Table 1 shows the demographic characteristics of the two groups with the mean age of the myopic group and the non-myopic group being 11.47 ± 2.4 years and 11.33 ± 2.8 years, respectively. Both groups showed 8 (26.7%) females and 22 (73.3%) males in each group. In the myopic group, the mean BMI was 17.42 ± 3.85, whereas in the non-myopic group, the mean BMI was 16.69 ± 2.99.

Table 1.

Demographic characteristics of the study population

	Myopic group (cases) n=30	Non-myopic group (control) n=30	P
Mean Age (years)	11.467	11.333	0.843
Sex/Gender
Male	22 (73.3%)	22 (73.3%)	1.000
Female	08 (26.7%)	08 (26.7%)
Mean BMI (kg/sq m)	17.417	16.686	0.415
Mean vit D3 value (ng/ml)	28.173	45.357	0.001*
Digital Screen time
<6 hrs	11 (36.7%)	17 (56.7%)	0.195
≥6 hrs	19 (63.3%)	13 (43.3)
Time spent outdoors
<2 hrs	10 (33.3%)	04 (6.6%)	0.097
≥2 hrs	20 (66.6%)	26 (86.7%)
Positive parental history of myopia#	8 (26.7%)	4 (13.3%)	0.333
Socioeconomic status (modified Kuppuswamy scale)
Upper lower	16 (53.3%)	12 (40%)	0.438
Upper middle	14 (46.7%)	18 (60%)

^#Parental history was taken positively with either of the parent or both being positive, *P value <0.05 is taken as significant

In terms of distribution of digital screen time, 11 (36.7%) children had a screen use of <6 hours and 19 (63.3%) children had a screen use of >6 hours in the myopic group, whereas 17 (56.7%) children had a screen use of <6 hours and 13 (43.3%) children had a screen use of >6 hours in the non-myopic group. In the myopic group, 16 (53.3%) children were from the upper-lower (lower) socioeconomic status as compared to 12 (40%) children in the non-myopic group. In relation to time spent outdoors (sun exposure), 10 (33.3%) and 04 (6.6%) children had an exposure time of <2 hours in the myopic group, whereas 20 (66.6%) and 26 (86.7%) children had an exposure time of >2 hours in the non-myopic group. In the myopic group, 8 (26.7%) children had a parental history of myopia, whereas in the non-myopic group, only 4 (13.3%) children gave a positive parental history.

In the myopic group, 21 (70%) children had low serum vit D3 levels (less than 30 ng/dl) and 9 (30%) children had normal serum vit D3 levels; however, in the non-myopic group, 8 (26.7%) children had low serum vit D3 levels and 22 (73.3%) children had normal serum vit D3 levels. This difference was statistically significant (P = 0.002) with a Pearson coefficient of 11.2 [Table 2].

Table 2.

Cross-tabulation demonstrating vit D3 levels in both the groups

Serum Vit D3 (ng/dl)	Myopic group	Non-myopic group	Total	P	Chi-square value
Low (<30 ng/dl)	21 (70.0%)	8 (26.7%)	29 (48.3%)	0.002*	11.279
Normal (≥30 ng/dl)	9 (30.0%)	22 (73.3%)	31 (51.7%)
Total	30	30	60

*P value <0.05 is taken as significant

Graph 1 depicts a significant correlation between SE and serum vit D3 levels, whereas no association was found between age and serum vit D3 levels. The association between serum vit D3 levels and SE showed a Pearson correlation value of 0.661. Univariant linear regression of the data establishes that myopia is associated with low serum vit D3 concentration (OR of 13.12, 95% CI 2.90–50.32, and a P value of 0.001). In our study, myopia does not show any significant association with sex, age, parental history of myopia, and sun exposure with an OR value of 1.57, 0.99, 2.25, and 0.68, respectively [Table 3].

Graph 1.

Correlation of 25(OH)D3 concentration (nmol/L) with (a) SE and (b) age

Table 3.

Linear Regression Analysis of the Associations with Myopia

Variables	OR (95% CI)	P
Serum Vit D3 status
Normal	Reference
Low	13.12 (2.90-59.32)	0.001*
Gender
Male	Reference
Female	1.57 (0.37-6.70)	0.542
Sun Exposure
≥2 hours	Reference
<2 hours	0.68 (0.15-3.17)	0.626
Parental history of myopia
No	Reference
Yes	2.25 (0.99-1.66)	0.341
Age (years)	0.99 (0.74-1.30)	0.884
BMI (kg/sq m)	1.29 (0.99-1.66)	0.626

*P value <0.05 is taken as significant

Subgroup analysis of serum vit D3 levels with gender showed that females are at higher risk of developing myopia them males. The mean serum vit D3 level was lower in children belonging to the upper-lower (lower) socioeconomic status and having a parental history of myopia [Graph 2].

Graph 2.

Subgroup analysis of vit D3 value with various variable (factors) that affects its level:(a) gender, (b) socioeconomic scale, (c) parental history of myopia, and (d) sun exposure

Discussion

As per the UNESCO, because multiple countries imposed nationwide school suspension, around 1.5 billion school-going children were affected.[17] A study during the COVID-19 pandemic has shown a progression of myopia even in children on atropine eye drops,[13] emphasizing the further evaluation of this progression.

In our study, myopic and non-myopic groups did not show any significant difference in terms of mean age, gender, BMI, and socioeconomic status. In this study of the Indian pediatric population, the low serum vit D3 level was strongly associated with recently detected myopia (P < 0.05). A meta-analysis study has proven the association of serum vit D3 with myopia, but it was performed in the adult population.[9] In our study, 70% of the myopic children had low serum vit D3 levels in contrast to only 26.7% of non-myopic children. Multiple hypotheses have been proposed to support this association. These include increased dopamine, altered intracellular calcium in ciliary muscles, and Vitamin D responsive element (VDRE)–retinoic acid complex-regulating growth of the sclera.[10,18-20] The latest hypothesis suggests an association between serum vit D3 levels and matrix metalloproteinases (MMPs), which in turn affects the scleral morphology and refraction.[21,22] In our study, the supplementary analysis showed a positive correlation between serum vit D3 levels and SE which further strengthens the hypothesis of hypovitaminosis D3 being a contributory factor for the development of myopia. Linear regression of the data displayed a significant association between myopia and the low value of serum vit D3 (depicted by a high odd ratio). Individuals with low serum vit D3 levels have approximately 13 times higher chances of developing myopia. Subgroup analysis of vit D3 among cases showed that females are at more risk of developing myopia as they have low serum vit D3 levels as compared to males. In both myopic and non-myopic groups, children with more hours of outdoor activities (i.e., increased sun exposure) have shown higher serum vit D3 levels, although the difference was not statistically significant. Children with a positive parental history of myopia had comparatively lower levels of serum vit D3, but the difference was not significant.

The lockdown imposed due to COVID-19 resulted in an inevitable increased screen use in school-going children (average of 5.24 hours/day).[23] Increased digital screen time involved online classes as well as recreational activities because all outdoor activities were restricted. Our study showed that >6 hours of screen time was found more in myopic children (63.3%) as compared to non-myopic children (43.3%). These findings were in accordance with earlier studies carried out on children and adults.[7,23,24] Increased screen time may cause myopia as it requires an increase in accommodation effort.[25,26] No significant association was found between vit D3 levels and digital screen time in the subgroup analysis.

Although all children had reduced outdoor activities, still our study reported that myopic children had relatively less time spent on outdoor activities in comparison to non-myopic children. This association is further verified by linear regression of data, displaying sun exposure as a protective factor for myopia development. The association of myopia with reduced outdoor activities is proven by former human[27,28] and animal studies.[29,30] Earlier studies have also emphasized the importance of outdoor activities.[31-33] Multiple propositions like the light dopamine hypothesis and relaxation of accommodation for distance focus have been postulated to explain this association.[16] A hypothesis that is still a debatable topic is sun exposure affecting serum vit D3 levels. Synthesis of vit D3 in the skin after exposure to UV-B radiation is the most substantial source of vit D; hence, it is difficult to distinguish it as an independent factor or a confounding factor for the development of myopia.[34] In our study, we have studied both as two independent factors and have tried to find their separate association with the development of myopia.

Myopia is a genetic disease with more than 200 genes and loci[35-37] being identified as accountable; hence, parental history of myopia is an important premonitory factor. In our study, 26.7% of myopic children had a parental history of myopia in either or both parents as compared to 13.3% of children in the non-myopic group. Linear regression of data in our study further supports this association with the development of myopia in children with positive parental history of myopia.[38] Our study reported that 53.3% of myopic and 40% of non-myopic children were from the upper-lower (lower) socioeconomic group as per the modified Kuppuswamy score. In our study, this association of myopia with lower socioeconomic status is further explained by low serum vit D3 levels in children from the lower socioeconomic group in comparison to the upper-middle group as already suggested by an earlier study.[39] The lower socioeconomic status affects the dietary intake of the children which in turn may cause multivitamin deficiency. Maybe already existing hypovitaminosis D3 in lower socioeconomic children got aggravated in the pandemic lockdown as outdoor activities and the income of parents both were restricted. It is supported by our study as subgroup analysis showed lower serum levels of vit D3 in children with a lower socioeconomic status. This outcome of our study suggests that serum vit D3 levels may be an autonomous factor for the development of myopia and not just a surrogate of sun exposure.

The strengths of this study are its high odd ratio and strong association found between low serum vit D3 level and myopia, although further studies are required to assess the applicability of these findings on larger samples and long-term follow-up of these children. This is the first study of its type in the Indian pediatric population. The small sample size and non-availability of quantitative measures of sun exposure are its limitations.

Conclusion

Our study reports that the low serum vit D3 level has a strong association with recently detected myopia in children. Even though it is a preliminary study, still it suggests the trial for Vit D3 supplementation in young children to delay or cease the development of myopia in post pandemic scenario. The supplementation trial should be carried out under the strict vigilance of a pediatrician, ensuring proper dosage and duration of vit D3 supplements.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.