Evaluation of the effect of patching therapy on dry eye tests and tear film osmolarity in children with amblyopia

Abstract

Background

To compare dry eye tests, meibography, and tear film osmolarity between eyes with and without patching therapy in amblyopic children and evaluate the effects of patching duration on these parameters.

Methods

Cooperative children aged between 4 and 12 years, with no history of ocular surgical intervention or ocular surface disease, who had been on patch therapy for at least 3 months due to monocular amblyopia, were included. Tear osmolarity was measured first, before any ocular surface manipulation, using the TearLab^® Osmolarity System (TearLab Corporation, San Diego, CA, USA). This was followed by tear film break-up time, fluorescein ocular surface staining, Schirmer 1 testing, and upper and lower eyelid meibography. Patients were divided into two groups based on daily patching duration (Group 1: 2–6 h/day, n = 21; Group 2: more than 6 h/day, n = 28). The findings were evaluated comparatively.

Results

A total of 98 eyes from 49 patients (22 females, 27 males), with a median age of 7 years (IQR: 5–8; range: 4–12), were included. There was no significant difference in age or gender between the two groups (p = 0.660, p = 0.089 respectively). T-BUT values were similar between the patched and unpatched amblyopic eyes [12 (10–13) vs. 12 (10–14) s; p = 0.129]. Oxford fluorescein staining also showed no significant between-eye difference (p = 1.000). Although osmolarity was higher in the patched eyes, this difference was not statistically significant (p = 0.162). There was no difference in median Schirmer values (p = 0.091). Although median osmolarity was higher and Schirmer 1 was lower in Group 2, these differences were not statistically significant (p = 0.396, p = 0.633 respectively). Upper and lower eyelid meibography results were categorized based on the presence or absence of any deterioration (Grade 0: No deterioration; Grades 1–3: Any deterioration). No significant differences were found in upper or lower eyelid meibography findings between the patched and unpatched amblyopic eyes (p = 1.000 and p = 0.210, respectively), or between Group 1 and Group 2 (p = 0.740 and p = 0.737, respectively).

Conclusion

Although patching is considered the gold standard for managing amblyopia, its effects on ocular surface homeostasis remain unclear. In this sample, no statistically significant differences were observed in dry eye tests, tear osmolarity, or meibography findings, and no measurable adverse effect on ocular surface parameters was demonstrated. Daily patching duration was also not significantly associated with these parameters. Larger prospective studies are needed to evaluate potential long-term effects.

Introduction

Amblyopia is characterized by a decrease in best-corrected visual acuity, affecting either one eye or, less commonly, both, and cannot be directly linked to any eye or visual pathway pathology. The main causes of amblyopia include strabismus, anisometropia, bilateral high refractive error, and deprivation. [1] It is the most common cause of monocular visual impairment in children. Its incidence is reported to be 1–5% worldwide and 2–4% in North America. [2, 3] A meta-analysis of 73 studies published in 2018 reported a prevalence of amblyopia at 1.75%, ranging from 0.51% in Africa to 3.67% in Europe. [4].

Amblyopia is a common childhood problem that significantly affects cognitive and motor development. However, it can be effectively treated through various methods during the critical period of visual development. [5–7] The main treatment options include occlusion, optical penalization, atropine, and levodopa. [8] In randomized controlled trials conducted by the Paediatric Eye Disease Investigator Group (PEDIG) to improve and standardize amblyopia treatment, it is reported that patching the better-seeing eye—used since the 1700s—remains the gold standard method. [9–13] Various results have been reported in the literature regarding the duration of patching that is sufficient for effective treatment. PEDIG studies have shown that 2 h/day of patching can provide visual improvement comparable to 6 h/day in moderate amblyopia, while 6 h/day can provide visual improvement comparable to full-time occlusion in severe amblyopia. Nevertheless, longer-duration and full-time patching regimens have also been evaluated in older children and those with profound amblyopia, with potential benefit reported in selected cases. [12–14] Known challenges with patching therapy include adherence problems, emotional and social side effects, reduced visual acuity in the patched eye, and skin irritation. [15].

Beyond its well-recognized clinical and psychosocial challenges, prolonged ocular occlusion may also influence ocular surface homeostasis and contribute to dry eye-related changes. Dry eye is a multifactorial disorder resulting from disturbances in tear production, tear evaporation, tear film stability, and ocular surface homeostasis. [16–18] Aqueous tear deficiency and evaporative mechanisms, particularly meibomian gland dysfunction and reduced blinking, may coexist and contribute to increased tear osmolarity, ocular surface inflammation, goblet cell loss, and tear film instability. [17–20] Ocular surface homeostasis may also be influenced by environmental and individual factors, including age, contact lens wear, prolonged near work, screen exposure, dry or air-conditioned environments, systemic diseases, medications, allergies, and previous ocular surgery. [21–24] In addition, closed-eye studies have shown that reduced tear turnover and prolonged eye closure may alter the physiological environment of the ocular surface and increase inflammatory components within the tear film. [25, 26] During amblyopia patching, reduced blinking and impaired tear film turnover may therefore theoretically affect meibomian gland function and ocular surface homeostasis, potentially contributing to dry eye symptoms or aggravation of pre-existing conditions such as blepharitis and allergic conjunctivitis, particularly with prolonged patching. [25, 26] However, ocular surface abnormalities directly attributable to amblyopia patching have rarely been reported, and, to the best of our knowledge, the effects of long-term patching on ocular surface parameters have not been systematically investigated.

Based on this information, this study aimed to compare the dry eye parameters, meibography, and tear osmolarity results of the patched eye and the unpatched amblyopic eye in children with amblyopia, and to evaluate how the duration of patching influences these parameters.

Materials and methods

This prospective, cross-sectional study included children aged 4 to 12 years who had been undergoing unilateral patching therapy for monocular amblyopia for at least 3 months, were able to cooperate with the measurements, and were reported by their caregivers to be adhering to the prescribed patching regimen. The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee (Approval no: 22-8.1T/66). Written informed consent was obtained from the legal guardians of all participating children. All children used adhesive eye patches, applied daily according to the prescribed duration. Adherence to the prescribed patching regimen was assessed based on caregiver reports. Patients with known serious ocular surface problems, such as allergic-vernal conjunctivitis, those using regular topical eye drops for any reason, contact lens wearers, individuals with autoimmune or rheumatological diseases, and those with a history of previous ocular surgery were excluded from the study.

All study-related evaluations were performed during a single study visit. All patients underwent a comprehensive ophthalmological examination, which included best-corrected visual acuity, biomicroscopic examination of the anterior and posterior segments, assessment of eye movements and strabismus, measurements of near and far deviation angles (if any), determination of stereopsis using the TNO test, and cycloplegic refraction. During the same visit, ocular surface assessment was performed after patients had remained without occlusion for at least 8–10 h. Before examination, patients remained in the room for at least 15 min to allow adaptation to ambient conditions. To minimize diurnal variation, all measurements were performed by the same clinician (Z.A.) in the same room, at the same temperature, between 10:00 AM and 12:00 PM. To minimize the potential influence of preceding tests on the ocular surface, all measurements were performed in a standardized sequence before cycloplegic drop instillation. First, tear osmolarity was measured in both eyes before the instillation of any eye drops or any ocular surface manipulation. Tear osmolarity was measured using the TearLab Osmolarity Device^® (TearLab Corporation, San Diego, CA, USA). Nanolitre tear samples were collected from the lower lateral meniscus with a probe attached to a disposable chip. The probe was then placed in a stationary reader to analyse the sample, and osmolarity values were recorded. A single valid measurement was recorded for each eye. If an invalid or error reading was obtained, the measurement was repeated using a new disposable test card. Routine electronic quality-control checks were performed according to the manufacturer’s recommendations. Fluorescein was then instilled, tear break-up time (T-BUT) was assessed, and ocular surface staining was graded according to the Oxford grading system. The Schirmer 1 test was subsequently performed. To evaluate meibomian gland morphology, upper and lower eyelid meibography images were obtained using the infrared imaging mode of the Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany). The images were independently evaluated by two masked clinicans (Z.A. and E.D.B.) according to the grading system described by Arita et al. [27], [28]. In cases of disagreement, the final grade was determined by consensus with a senior cornea specialist (M.P.). The Ocular Surface Disease Index (OSDI) questionnaire was planned to assess subjective symptoms. However, due to the age group, patients were unable to complete it, and reliable results were not obtained.

All measurements were obtained from both eyes. The eye receiving occlusion was defined as the “patched eye,” whereas the contralateral amblyopic eye not receiving occlusion was defined as the “unpatched amblyopic eye.” Daily patching duration was defined as the prescribed duration of occlusion per day (hours/day). Total duration of patching therapy was defined as the period from initiation of patching therapy to ocular surface assessment and was expressed in months. Daily patching duration was determined as part of routine clinical care before the study visit. Longer daily patching (> 6 h/day) was used in selected cases, including children with profound amblyopia or those approaching the later stages of visual development. Patients were divided into two groups based on daily patching duration (Group 1: 2–6 h per day, Group 2: more than 6 h per day). The results were compared both between the patched and unpatched amblyopic eyes and according to the patching duration (Groups 1 and 2).

Statistical analysis

Data were analysed using IBM SPSS Statistics 25.0 (IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.). The suitability of variables for normal distribution was assessed with the Shapiro-Wilk test. It was found that the variables did not follow a normal distribution. Therefore, continuous variables were presented as medians and interquartile ranges (IQRs) in the descriptive statistics.

The Wilcoxon signed-rank test was used for paired comparisons between the patched and unpatched amblyopic eyes, whereas the Mann-Whitney U test was used for comparisons between Group 1 and Group 2. Hodges-Lehmann median differences with 95% confidence intervals were reported as effect estimates.

Oxford fluorescein staining scores were presented descriptively by grade. McNemar’s test was used for paired categorical comparisons between the patched and unpatched amblyopic eyes. Meibography scores were dichotomized as Grade 0 (no gland loss) versus Grades 1–3 (any gland loss) for categorical comparisons because of the small number of eyes with higher-grade gland loss, while the original Grade 0–3 distributions were also presented descriptively. McNemar’s test was also used for upper- versus lower-eyelid meibography comparisons within the same eye, with matched-pairs odds ratios reported as effect estimates. The chi-square test was used for meibography comparisons between Group 1 and Group 2, with Yates continuity correction applied when appropriate. Original Grade 0–3 meibography scores were additionally analysed using mixed-effects ordinal logistic regression models with a patient-level random intercept to account for within-patient dependence while preserving the ordinal nature of the data.

Spearman’s rho correlation analysis was used to assess relationships between continuous variables. A p-value of < 0.05 was considered statistically significant.

Results

A total of 98 eyes from 49 patients participated in this prospective, cross-sectional study. The median age was 7 years (IQR: 5–8; range: 4–12), and the male-to-female ratio was 27/22. The median total duration of patching therapy was 18 months (IQR: 7–25). When patients were grouped according to daily patching duration, 21 patients (F/M: 6/15) were included in Group 1 (2–6 h/day), whereas 28 patients (F/M: 16/12) were included in Group 2 (> 6 h/day).

Anterior segment examination revealed juvenile cataracts in two patients that did not require surgery and an old, inactive stromal corneal opacity in one patient. Fundoscopy revealed morning glory anomaly in one child. The most common indication for patching was strabismic amblyopia, followed by anisometropia and deprivation (Table 1). The distribution of amblyopia severity according to the best-corrected visual acuity of the amblyopic eye at the study visit is presented in Table 2. The median best-corrected visual acuities of the unpatched amblyopic and patched eyes were 0.7 (IQR: 0.6–0.8) and 0.9 (IQR: 0.8-1.0), respectively [p < 0.001, Median Difference (95% CI): -0.2 (-0.25 to -0.15)]. The median T-BUT was 12 (IQR: 10–13) seconds in the patched eyes and 12 (IQR: 10–14) seconds in the unpatched amblyopic eyes, with no significant between-eye difference (p = 0.129). Oxford fluorescein staining was Grade 0 in 41 (83.7%), Grade 1 in 6 (12.2%), and Grade 2 in 2 (4.1%) patched eyes, whereas it was Grade 0 in 42 (85.7%) and Grade 1 in 7 (14.3%) unpatched amblyopic eyes, with no Grade 2 or higher staining observed. Any staining (Grade ≥ 1) was observed in 8 (16.3%) and 7 (14.3%) eyes, respectively, with no significant between-eye difference (p = 1.000). No correlation was found between osmolarity and Schirmer values with age or gender (p > 0.05 for all). Although osmolarity was higher in the patched eyes, the difference was not statistically significant (p = 0.162). There was no difference in the median Schirmer values (p = 0.091) (Table 3).

Table 1.

Causes of amblyopia in children receiving patching therapy

Etiologies of Amblyopia	n (%)
Strabismic Amblyopia	36 (73.46%)
Accommodative Refractive Esotropia	10 (20.4%)
Monocular Esotropia	8 (16.32%
Alternating Esotropia	7 (14.28%)
Intermittent Exotropia	4 (8.16%)
Duane Retraction Syndrome	3 (6.12%)
Monocular Exotropia	2 (4.08%)
Congenital Esotropia	1 (2.04%)
Partial Accommodative Refractive Esotropia	1 (2.04%)
Anisometropic Amblyopia	5 (10.20%)
Deprivation amblyopia	3 (6.12%)
Juvenile Cataract	2 (4.08%)
Corneal Opacity	1 (2.04%)
Meridional Amblyopia	2 (4.08%)
Isoametropic Amblyopia	1 (2.04%)
Other Pathologies	2 (4.08%)
Morning Glory Syndrome	1 (2.04%)
Marcus Gunn Jaw Winking Syndrome	1 (2.04%)
Total	49 (100%)

Table 2.

Distribution of amblyopia severity according to amblyopic-eye best-corrected visual acuity at the study visit

Amblyopia severity at the study visit	BCVA	n (%) (49 patients)
Better than 20/40	Better than 20/40 (> 0.50)	35 (71.4%)
Moderate amblyopia	20/40 − 20/80 (0.25–0.50)	9 (18.4%)
Severe amblyopia	20/100 − 20/400 (0.05–0.20)	5 (10.2%)

BCVA: best-corrected visual acuity. Amblyopia severity was categorized according to amblyopic-eye BCVA at the study visit: moderate amblyopia, 20/40 − 20/80; severe amblyopia, 20/100 − 20/400. Eyes with BCVA better than 20/40 were reported separately. [36] Because patients were already undergoing patching therapy at the time of assessment, these categories reflect amblyopia severity at the study visit rather than pretreatment severity

Table 3.

Comparison of ocular surface parameters between the patched and unpatched amblyopic eyes and according to daily patching duration

	Patched Eye Median (IQR) (n = 49)	Unpatched Amblyopic Eye Median (IQR) (n = 49)	Hodges-Lehmann Median Difference (95% Confidence Interval)	p-value
Osmolarity (mOsm/L)	282 (278–291)	280 (276–289)	-1.5 (-4.0 to 0.5)	0.162*
Schirmer 1 (mm)	20 (14–23)	20 (16–23)	1.0 (0.0 to 2.5)	0.091*
T-BUT (s)	12 (10–13)	12 (10–14)	0.0 (0.0 to 0.5)	0.129*
Oxford Corneal Staining Any staining (Grade ≥ 1), n (%) Grade 0, n (%) Grade 1, n (%) Grade 2, n (%) Grade ≥ 3, n (%)	8 (16.3%) 41 (83.7%) 6 (12.2%) 2 (4.1%) 0 (0.0%)	7 (14.3%) 42 (85.7%) 7 (14.3%) 0 (0.0%) 0 (0.0%)		1.000*
	Group 1 (n = 21 patients)	Group 2 (n = 28 patients)
Osmolarity (mOsm/L)	282 (278–287)	284 (279–296)	-1.5 (-5.5 to 1.5)	0.396†
Schirmer 1 (mm)	20 (13–23)	19 (14–22)	1.5 (-0.5 to 3.5)	0.633†
T-BUT (s)	11 (10–13)	12 (10–13)	0.0 (-2.0 to 1.0)	0.575†

Values are presented as median (IQR) unless otherwise indicated. Oxford fluorescein staining results are presented as n (%). *Wilcoxon Signed-Rank test was used for paired continuous variables, and McNemar’s test was used for paired categorical variables. †Mann-Whitney U test was used for comparisons between Group 1 and Group 2. Group 1: 2–6 h/day; Group 2: >6 h/day. One patched eye per patient was included in the group comparisons

Meibography results were categorized based on whether deterioration was present (Grade 0: No deterioration, Grades 1–3: Any deterioration). Deterioration was observed in the upper lid in 45% of patched eyes and in the lower lid in 59%, while in unpatched amblyopic eyes, it was present in the upper lid in 45% and in the lower lid in 47% (Table 4). Mixed-effects ordinal logistic regression using the original Grade 0–3 meibography scores showed no significant difference between the patched and unpatched amblyopic eyes for either the upper eyelid (OR = 1.19, 95% CI: 0.51–2.78; p = 0.691) or the lower eyelid (OR = 1.91, 95% CI: 0.85–4.30; p = 0.119). Similarly, no significant differences were observed between Group 2 and Group 1 in the patched eyes for the upper eyelid (OR = 0.77, 95% CI: 0.16–3.59; p = 0.736) or the lower eyelid (OR = 0.96, 95% CI: 0.22–4.17; p = 0.961). When upper and lower eyelid meibography findings were compared within the same eye, gland loss was more frequent in the lower than in the upper eyelid of the patched eyes [29/49 (59.2%) vs. 22/49 (44.9%)], however, the difference was not statistically significant (matched-pairs OR = 2.40, p = 0.143). In the unpatched amblyopic eyes, the corresponding rates were 23/49 (46.9%) and 22/49 (44.9%), with no significant difference (matched-pairs OR = 1.11, p = 1.000).

Table 4.

Distribution of meibography grades in patched and unpatched amblyopic eyes and in patient groups defined by daily patching duration

Meibography	Patched Eye(n=49)	Unpatched Amblyopic Eye(n=49)	p value
Upper Eyelid
Grade 0	27 (55%)	27 (55%)
Grade 1	15 (31%)	18 (37%)
Grade 2	6 (12%)	3 (6%)
Grade 3	1 (2%)	1 (2%)
Grades 1-3 (any gland loss)	22 (45%)	22 (45%)	1.000*
Lower Eyelid
Grade 0	20 (41%)	26 (53%)
Grade 1	23 (47%)	21 (43%)
Grade 2	6 (12%)	1 (2%)
Grade 3	0 (0%)	1 (2%)
Grades 1-3 (any gland loss)	29 (59%)	23 (47%)	0.210*
	Group 1(n=21 patients)	Group 2(n=28 patients)
Upper Eyelid
Grade 0	11 (52%)	16 (57%)
Grade 1	7 (33%)	8 (29%)
Grade 2	2 (10%)	4 (14%)
Grade 3	1 (5%)	0 (0%)
Grades 1-3 (any gland loss)	10 (48%)	12 (43%)	0.740**
Lower Eyelid
Grade 0	8 (38%)	12 (43%)
Grade 1	11 (52%)	12 (43%)
Grade 2	2 (10%)	4 (14%)
Grade 3	0 (0%)	0 (0%)
Grades 1-3 (any gland loss)	13 (62%)	16 (57%)	0.737**

*McNemar test for comparisons between patched and unpatched amblyopic eyes. **Chi-square test for comparisons between Group 1 and Group 2. Group 1: daily patching duration of 2-6 hours/day; Group 2: daily patching duration of >6 hours/day. Groups 1 and 2 were defined at the patient level according to daily patching duration; one patched eye per patient was included in the group comparisons

When patients were compared according to daily patching duration, no significant differences were found between the groups in terms of age and gender (p = 0.660, p = 0.089, respectively). Although median osmolarity was higher and Schirmer 1 was lower in Group 2, the differences were not statistically significant (p = 0.396, p = 0.633, respectively) (Table 4 3). No significant differences were found between Group 1 and Group 2 in upper or lower eyelid meibography findings (p = 0.740 and p = 0.737, respectively) (Table 4). When all subjects were analysed, no significant correlation was found between the total duration of patching therapy and tear osmolarity in either the patched eyes (rho = 0.029, p = 0.850) or the unpatched amblyopic eyes (rho=-0.058, p = 0.705).

Discussion

Studies directly examining the effects of amblyopia patching on ocular surface homeostasis are limited; however, previous closed-eye studies suggest a possible biological mechanism. Frucht-Pery et al.²⁵ reported that eye closure alters the physiological environment of the cornea and conjunctiva, with reduced reflex tear secretion, increased secretory IgA levels, and activation of complement C3, resulting in subclinical inflammation. Similarly, Sack et al.²⁶ demonstrated that reduced tear film turnover was associated with increased secretory IgA, polymorphonuclear leukocytes, and pro-inflammatory cytokines, creating an inflammatory ocular surface environment. These findings suggest that prolonged ocular occlusion may theoretically influence tear film homeostasis, although whether comparable changes occur during amblyopia patching remains unclear.

Clinical observations from conditions involving prolonged corneal coverage provide additional indirect support for this mechanism. Filamentous keratitis has been described in conditions in which the ocular surface remains largely covered by the eyelid, such as double elevation palsy and wide-angle strabismus. [29, 30] These filaments contain mucin, inflammatory cells, and conjunctival and corneal epithelial cells, and their formation has been attributed to increased friction between the cornea and eyelid during blinking. [29, 30] Similar mechanisms may also be relevant during patching therapy, as reduced blinking and impaired tear film turnover may contribute to disruption of ocular surface homeostasis.

Tear film osmolarity is an objective numerical measure of ocular surface homeostasis and is widely used in the assessment of dry eye disease. [31–33] Normal tear film osmolarity is reported to be around 299–301 mOsm/L, while in dry eyes it increases to 325–340 mOsm/L. [34] In the presented study, osmolarity in both the patched eye and the unpatched amblyopic eye was approximately 280 mOsm/L, with no statistically significant difference between them and values well below those reported in the literature for dry eye. Additionally, no significant correlation was observed between the total duration of patching therapy and tear osmolarity when the entire study population was analysed. In detecting meibomian gland dysfunction, the grading scale described by Arita et al.²⁸ provides an objective perspective. In this study, patients were divided into groups based on whether their meibomian glands were affected (Grade 0 and Grade 1, 2, or 3). No significant difference was found between the patched and the unpatched amblyopic eyes, or when patients were grouped according to daily patching duration (Groups 1 and 2). Consistent with the dichotomized analyses, mixed-effects ordinal logistic regression using the original Grade 0–3 meibography scores also showed no significant differences between the patched and unpatched amblyopic eyes or between the daily patching-duration groups.

Several limitations of this study should be considered. An important limitation is its cross-sectional design and the absence of ocular surface measurements before the initiation of patching therapy. Therefore, although the unpatched amblyopic eye served as an intra-individual comparator, the observed between-eye findings cannot establish temporal changes or causal effects attributable to patching. As is well known, one of the biggest challenges of patching therapy for amblyopia is patient compliance. Studies using objective compliance measurements show that most patients receive significantly less treatment than prescribed. [35] In the present study, actual adherence to the prescribed daily patching duration was not objectively monitored using occlusion dose monitors or other methods; instead, adherence was based on caregiver reports. Furthermore, subjective symptoms could not be reliably evaluated using the OSDI questionnaire because of the age of the study population.

Another limitation is the small sample size of 49 patients and the absence of an a priori power calculation. Therefore, the non-significant findings should not be interpreted as evidence of equivalence or absence of an effect, as limited statistical power may have contributed to the lack of statistically significant differences. Additionally, the presence of structural ocular abnormalities in a small number of unpatched amblyopic eyes may have contributed to the clinical heterogeneity of the study population. Because daily patching duration reflected clinically prescribed treatment rather than a study-assigned intervention, confounding by indication cannot be excluded. Therefore, comparisons according to daily patching duration should not be interpreted as evidence of an independent causal dose-response effect. Results may differ in larger studies that include tear proteomics analysis and biomarker assessment.

In conclusion, no statistically significant differences were observed between the patched and unpatched amblyopic eyes in T-BUT, ocular surface staining, tear osmolarity, Schirmer test results, or meibography findings. Daily patching duration and total duration of patching therapy were also not significantly associated with the evaluated ocular surface parameters. These findings suggest that occlusion therapy, which remains a fundamental treatment for amblyopia, was not associated with a measurable adverse effect on ocular surface parameters in this sample. However, the results should be interpreted cautiously given the relatively small sample size, and larger prospective studies are needed to clarify the potential long-term effects of occlusion on ocular surface homeostasis. Nevertheless, if ocular surface discomfort develops during treatment, its potential to negatively affect treatment compliance in children should be kept in mind, and symptomatic treatment with artificial tears may be considered when clinically indicated.

Abbreviations

PEDIG

Paediatric Eye Disease Investigator Group

T-BUT

Tear break-up time

OSDI

Ocular Surface Disease Index

IQRs

Interquartile ranges

z-DEWS

Dry Eye Workshop

BCVA

Best-corrected visual acuity

OR

Odds ratio

CI

Confidence interval

Author contributions

Z.A. and E.D.B.: writing of the manuscript, Z.A. and E.D.B.: Data gathering and statistics, E.D.B. and M.P.: Design of the study and revision.

Funding

The study was carried out with the financial support of the Ege University Office of Scientific Research Projects (Project ID: 24181).

Data availability

The data used in this study will be provided by the corresponding author upon a reasonable request.

Declarations

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki, and approval was obtained from Ege University Ethics Committee for Medical Studies (Approval no: 22-8.1T/66). Written informed consent was obtained from the legal guardians of all participating children.

Consent for publication

Written informed consent was obtained from the legal guardians of all participating children.

Competing interests

The authors declare no competing interests.