Is allergic conjunctivitis associated with health-related quality of life in children and their parents?
This case-control study including 188 children and their parents noted that allergic conjunctivitis had an association with reduced health-related quality of life for both children and their parents. This reduction was most prominent in children with vernal keratoconjunctivitis and atopic keratoconjunctivitis.
The findings of this study suggest a multifaceted association of allergic conjunctivitis with quality of life; detailed assessment of quality of life for improved care of pediatric patients with chronic allergic conjunctivitis would be useful.
Allergic conjunctivitis (AC) is one of the most common allergic diseases and is especially problematic in children and adolescents. The course of AC is generally prolonged and often recurs. Understanding the health-related quality of life (QOL) of both children with AC and their parents would be useful.
To evaluate the association between AC and health-related QOL in children and their parents.
Design, Setting, and Participants
A prospective case-control study was conducted at Zhongshan Ophthalmic Center, a single tertiary referral center, from November 16, 2019, through January 20, 2020. Participants comprised 92 children aged 5 to 18 years with AC and their parents and 96 healthy, age-matched children who served as controls and their parents. The 92 children in the AC group were subdivided into cohorts with vernal keratoconjunctivitis (VKC) (23 [25.0%]) or atopic keratoconjunctivitis (AKC) (7 [7.6%]) and seasonal allergic conjunctivitis (SAC) (26 [28.3%]) or perennial allergic conjunctivitis (PAC) (36 [39.1%]).
Main Outcomes and Measures
Pediatric Quality of Life Inventory, version 4.0 (PedsQL), scores for children and their parents. Scores range from 0 to 100, with higher scores indicating better health-related QOL and fewer negative aspects.
In the AC group, 77 of 92 (83.7%) participants were boys, and 67 (72.8%) of the parents were women. Of the individuals in the control group, 55 of 96 (57.3%) of the children were girls and 76 (79.2%) of the parents were women. Median total PedsQL scores were reduced in both children with AC (69.6 [interquartile range [IQR], 66.3-72.8 vs 96.7; IQR, 92.7-98.9; P < .001) and their parents (68.8; IQR, 63.9-71.4 vs 96.5; IQR, 95.1-97.9; P < .001). The reduction in health-related QOL was more severe in children with VKC/AKC than in those with SAC/PAC (difference, –3.3; 95% CI, –5.4 to –1.1; P = .004) and their parents (difference, –4.3; 95% CI, –7.1 to –2.1; P < .001). In the AC group, a higher corneal fluorescein staining score was associated with lower QOL in children (β, –1.16; 95% CI, –1.80 to –0.52; P = .001); higher corneal fluorescein staining scores (β, –1.12; 95% CI, –1.74 to –0.50; P = .001) and multiple clinical consultations (β, –3.96; 95% CI, –7.34 to –0.57; P = .02) were associated with lower QOL in parents. The parents' QOL scores were correlated with their children's QOL scores (correlation coefficient, r = 0.59; P < .001).
Conclusions and Relevance
These findings suggest AC has a negative association with health-related QOL for children and their parents, especially in children with VKC/AKC or higher corneal fluorescein staining scores.
The World Health Organization has stated that chronic conditions are one of the major health care challenges of the 21st century.1,2 Furthermore, the World Health Organization has emphasized that health care for individuals with chronic conditions should be reoriented to focus on the patients and their families.1,2 Allergy is a common chronic condition with a substantially increasing worldwide prevalence.3,4 This condition has become a major public health issue that negatively affects the quality of life (QOL) and generates significant social expense as reported by the World Allergy Organization.5-7 Allergic conjunctivitis (AC) is one of the most common allergic diseases. The morbidity of AC is especially problematic in children and adolescents, and has gradually become one of the most prevalent eye disorders in children.8 Allergic conjunctivitis is conjunctival hypersensitivity to allergen stimulation, mainly including types I and IV hypersensitivity.9,10 The prevalence of AC is 40% in the US and 15% to 20% in Japan.11,12 The 2 most common types of AC are perennial AC (PAC) and seasonal AC (SAC), with a combined prevalence of 74% to 95%; vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are relatively rare but more severe.8,13-15
In addition to visual function, the eye plays a role in one’s psychological, emotional, and subconscious status.14,16 It has been reported that chronic eye diseases, such as dry eye, Graves orbitopathy, and childhood glaucoma,17-19 may affect patients' sleep, mood, and QOL. Allergic conjunctivitis tends to have a chronic course with multiple recurrent episodes,8 and many patients need to seek medical consultation repeatedly, which may further adversely affect their QOL. Therefore, AC may generate worry, anxiety, depression, or other psychological stress for patients and their family members.
Reduced QOL has been reported in adults with SAC20 and in children with VKC in an uncontrolled study with a small sample.21 To our knowledge, neither of these studies focused on children—the patient population most affected by AC—and these studies did not discuss these patients’ parents. Whether the QOL of children with AC and their parents will be affected is unknown. Herein, we report on a prospective case-control study conducted to evaluate the association of AC with the QOL of children and their parents.
This prospective case-control study was conducted at Zhongshan Ophthalmic Center from November 16, 2019, through January 20, 2020, in accordance with the tenets of the Helsinki Declaration of Human Studies22 and was approved by the ethics committee of Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. We addressed any questions before obtaining written informed consent from all parents and assent from all children. We screened the medical records of all children who visited our keratopathy clinics in advance to identify children who may meet the inclusion criteria. After informed consent was obtained, those who met the criteria were enrolled in the study. Families were offered no incentives or compensation. For those who did not want to participate, we recorded the reasons given. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Children with AC aged 5 to 18 years and their parents were enrolled. The diagnosis of AC was based on the diagnostic criteria of the American Academy of Ophthalmology for conjunctivitis.12,15 Patients with the following conditions were excluded: inability to communicate, a history of allergies to fluorescein, the occurrence of any other ocular disorders (except mild ametropia), a history of ocular surgery or trauma within the past 3 months, and a history of mental disorders or systemic diseases, such as diabetes, kidney disease, and heart disease. Healthy children serving as controls and their parents were recruited from those receiving routine ophthalmic examination or refraction correction. Healthy children with the following conditions were excluded: inability to communicate, a history of allergies to fluorescein, the occurrence of any other ocular disorders (except mild ametropia), and a history of ocular surgery or trauma within the past 3 months, mental disorders, or systemic diseases. As for parents, the questionnaire was intended for the primary caregiver (ie, the caregiver who spends more time with the child); in cases of equal parenting, either parent could be enrolled. The exclusion criteria for parents in both the AC and control groups were a history of mental disorders or ocular and systemic diseases and the recent occurrence of a major life-altering event. Participants in the AC group were divided into VKC/AKC and SAC/PAC subgroups according to the different underlying mechanisms.
We approached 120 children with AC and their parents and 137 healthy children and their parents who met the inclusion criteria; 22 children and their parents in the AC group and 31 children and their parents in the control group declined because of a perceived lack of time to complete the questionnaires. We also excluded 6 children and their parents in the AC group and 10 children and their parents in the control group because they did not complete the questionnaires after giving consent or could not cooperate. The statistical analysis was performed for the remaining 92 children with AC and 96 healthy children and their parents (Figure 1).
A complete medical and ophthalmic history was collected from all participants. Children received slitlamp and refraction examination, and best-corrected visual acuity was measured in both eyes. Conjunctival hyperemia, papillary, and follicle formation were evaluated and graded according to scales proposed in the Japanese Guidelines for Allergic Conjunctival Diseases 2017.12 Corneal fluorescein staining (CFS)23 and corneal pathologic characteristics24 were evaluated and graded as well. Two physicians (S.-y.Z. and J.L.) were responsible for examinations and questionnaires separately.
Pediatric Quality of Life Inventory, version 4.0 (PedsQL), was used to assess the QOL of children and their parents. The reliability and validity of the Chinese version of the PedsQL have been verified, and the tool is widely used in the study of Chinese populations.25-27 The PedsQL tool is a standardized, generic assessment of health-related perceptions of QOL in pediatric patients and provides different aspects of measuring QOL for patients and their parents.25-28 The PedsQL tool has been used to evaluate the QOL of patients with conditions such as glaucoma,28 strabismus,29 uveitis,30 and corrective lenses wear.31 The PedsQL Child Self-report contains 23 items covering 4 subscales: physical, emotional, social, and school functioning. The latter 3 subscales represent psychosocial health. The report is specific to the age of the child, covering children aged 2 to 4, 5 to 7, 8 to 12, and 13 to 18 years. The PedsQL Family Impact Module for parents contains 36 questions that evaluate 8 subscales: physical functioning, emotional functioning, social functioning, cognitive functioning, communication, worry, daily activities, and family relationships. Scores range from 0 to 100, with higher scores indicating better health-related QOL and fewer negative aspects.
Based on the primary outcome of the QOL total score, a sample size of 86 children per group was required to achieve 90% power to detect a mean difference of −15.0 under an assumption of mean QOL scores of 75.0 in the AC group and 90.0 in the control group, and a common SD of 30.0, at a 2-sided significance level of α = .05, using a 2-sample t test. The sample size was calculated using PASS, version 16.0 (NCSS Statistical Software).
Both eyes were tested for all clinical parameters; the side with a greater severity of AC was used for analysis. When the eyes were comparable, the right eye was chosen. We applied descriptive statistics throughout, reporting means (SDs) for normally distributed data or medians and interquartile ranges (IQRs) for data not normally distributed. Best-corrected visual acuity was converted from Snellen units to logMAR values for analysis. The spherical equivalent (SE) of the refractive error was calculated as the spherical value plus half of the cylindrical (astigmatic) value. We compared the differences between the 2 groups by using independent-samples t test or rank sum test. Differences between groups were assessed using nonparametric Kruskal-Wallis tests. Univariable and multivariable linear regression models were fit to identify risk factors that might be correlated with QOL at enrollment. To determine the precision of our estimation of the difference, we also calculated the 95% CI around the median difference. P values were not adjusted for multiple comparisons and a 2-sided test was used with findings significant at P < .05. All statistical analyses were performed using SPSS software, version 25.0 (IBM SPSS).
The proportion of missing data was low. No data were missing for age, sex, best-corrected visual acuity, and SE. Disease duration of the eye condition could not be determined exactly in 2 children (2.2%) in the AC group. For all questionnaires administered, response and completion rates were high. Five participants (5.4%) did not know the history of other allergic diseases and 32 participants (34.8%) did not know the allergens.
A total of 92 children with AC and 96 healthy children were enrolled with their parents. The mean (SD) ages were matched between the 2 groups (children: 9.25 [2.81] vs 9.31 [2.73] years; P = .48; parents: 37.19 [4.79] vs 36.70 [5.11] years; P = .48) (Table 1). In the AC group, 77 of the 92 participants (83.7%) were boys, 15 (16.3%) were girls, and 67 (72.8%) of the parents were women, in the control group, 55 of the 96 participants (57.3%) were girls, 41 (42.7%) were boys, and 76 (79.2%) of the parents were women.
The mean (SD) best-corrected visual acuity (0.008 [0.05] vs 0.015 [0.05]; P = .07) and the median SE (–0.75; IQR, –2.13 to 0.38 vs –0.75; IQR, –2.13 to 0.38; P = .90) were comparable in the 2 groups (Table 1). In the AC group, PAC (36 of 92 [39.1%]) was the most common type followed by SAC (26 of 92 [28.3%]), VKC (23 of 92 [25.0%]), and AKC (7 of 92 [7.6%]). The median disease duration was 12.00 (IQR, 6.00-28.50) months, and 71.7% (66 of 92) of the children with AC had been treated previously. Detailed ocular conditions are reported in Table 1. The most common comorbidity with AC was rhinitis (46 of 53 [86.8%] children), followed by eczema (9 of 53 [16.9%] children).
The median total PedsQL scores were lower for both children and their parents in the AC group compared with those in the control group (children: 69.6; IQR, 66.3-72.8 vs 96.7; IQR, 92.7-98.9; P < .001; parents: 68.8; IQR, 63.9-71.4 vs 96.5; IQR, 95.1-97.9; P < .001) (Figure 2). The median subscores of the physical functioning (75.0; IQR, 75.0-75.0 vs 100.0; IQR, 100.0-100.0; P < .001), emotional functioning (65.0; IQR, 55.0-75.0 vs 100.0; IQR, 90.0-100.0; P < .001), social functioning (75.0; IQR, 70.0-75.0 vs 100.0; IQR, 95.2-100.0; P < .001), and school functioning (65.0; IQR, 56.3-70.0 vs 90.0; IQR, 85.0-95.8; P < .001) scales were lower in children with AC compared with the controls (Table 2). A similar finding was observed in the different aspect in parents (Table 2). The median subscores of physical functioning (66.7; IQR, 58.3-75.0 vs 100.0; IQR, 100.0-100.0; P < .001), emotional functioning (70.0; IQR, 60.0-75.0 vs 100.0; IQR, 95.0-100.0; P < .001), social functioning (75.0; IQR, 64.1-75.0 vs 100.0; IQR, 100.0-100.0; P < .001), cognitive functioning (75.0; IQR, 75.0-75.0 vs 100.0; IQR, 100.0-100.0; P < .001), communication (75.0; IQR, 75.0-75.0 vs 100.0; IQR, 100.0-100.0; P < .001), worry (55.0; IQR, 45.0-60.0 vs 80.0; IQR, 70.0-90.0; P < .001), and family functioning (75.0; IQR, 66.0-75.0 vs 100.0; IQR, 100.0-100.0; P < .001) summary scores were lower in parents of children in the AC group compared with the control group. There was no significant age difference of the QOL scores in the AC group (Table 3). The reduction in emotional functioning of children and the reduction in physical functioning of parents were most substantial (Table 2).
Different subtypes of AC were further analyzed. Children with VKC/AKC (difference, –3.3; 95% CI, –5.4 to –1.1; P = .004) and their parents (difference, –4.3; 95% CI, –7.1 to –2.1; P < .001) had worse QOL than those with SAC/PAC (Figure 2). Subscores of emotional functioning (difference, –5.0; 95% CI, –10.0 to 0; P < .001; P = .02) and school functioning (difference, –5.0; 95% CI, –10.0 to 0; P = .02) in children with VKC/AKC and physical functioning (difference, –8.3; 95% CI, –12.5 to –4.2; P = .002), emotional functioning (difference, –5.0; 95% CI, –10.0 to 0; P = .04), and worry (difference, –10.0; 95% CI, –15.0 to –5.0; P < .001) in parents were also found to be lower than those in children with SAC/PAC and their parents (Table 2).
Correlation Between QOL and Potential Influencing Factors
Univariate linear regression showed that children’s QOL in the AC group was correlated with disease duration (β, –0.08; 95% CI, –0.16 to 0; P = .046), severe palpebral conjunctiva hyperemia (β, –2.15; 95% CI, –4.17 to –0.13; P = .04), and a high CFS score (β, –1.29; 95% CI, –1.87 to –0.71; P < .001); parents’ QOL in the AC group was correlated with multiple consultations (β, –4.76; 95% CI, –8.41 to –1.11; P = .01), severe bulbar conjunctiva hyperemia (β, –2.33; 95% CI, –4.41 to –0.25; P = .03), and a high CFS score (β, –1.31; 95% CI, –1.90 to –0.72; P < .001). In the final multivariate model, children’s QOL was correlated only with a high CFS score (β, –1.16; 95% CI, –1.80 to –0.52; P = .001). Parents’ QOL was correlated with a higher CFS score (β, –1.12; 95% CI, –1.74 to –0.50; P = .001) and multiple consultations (β, –3.96; 95% CI, –7.34 to –0.57; P = .02) (Table 3). The QOL of children and their parents was found to be correlated as well (correlation coefficient r = 0.59; P < .001). However, multiple previous consultations and disease duration had no correlation with the QOL of children. Furthermore, age, disease duration, conjunctival hyperemia, and educational level of the parents were found to have no correlation with the QOL of children and parents.
Although the QOL of patients with AC has been reported,20,32-35 to our knowledge, none of these studies focused on children, which is the patient population most affected by AC. In addition, these studies did not discuss whether there were any associations between AC and these patients’ parents. In these studies, only VKC or SAC, rather than all types of AC as a whole, were investigated. Furthermore, most of these studies were uncontrolled. We conducted a case-control study to investigate the association of AC with QOL as a whole and its subtypes on children and their parents for the first time to our knowledge by using PedsQL, which is specific to children and provides different aspects of measuring QOL for children as well as for their parents.28,36-38 Reliability and validity for Chinese Version of PedsQL have been verified and the tool is widely used in the study of Chinese populations.25-27 Our results showed that the QOL of pediatric patients with AC and their parents were both decreased, and such impairment was associated with the severity of corneal complications. In the different aspects of QOL, the score of school functioning was the lowest. Because children generally spend most of their time in the school environment, this outcome raises an issue regarding whether children have a poorer performance in their education.
An unexpected finding was that the decrease of QOL in children with AC was worse than in previous studies of children diagnosed with blinding diseases, such as glaucoma and congenital cataract,28,39 in which the same PedsQL questionnaires had been used. Although there are cultural differences, continuous eye discomfort and the recurrent nature of AC may contribute to a worsened QOL. Compared with the improvement in QOL of children with glaucoma as they aged,28 such a change was not noted in children with AC.
To our knowledge, our study is the first noting that QOL was also impaired in parents of children with AC, especially in those with VKC/AKC, and such impairment was associated with the impairment noted in their children. Among all subscores of parents’ QOL, worry was the lowest and the issue worrying parents most was whether the treatment would be effective. This finding suggests that more communication with parents regarding treatment and prognosis is needed. A higher CFS score in children and multiple consultations were correlated with poorer parental QOL. Generally, multiple consultations indicate a more refractory or multiple recurrent status of AC and/or more care about their children, which might subsequently generate more anxiety or stress.
This study has limitations. First, it was conducted in the cornea clinic of a tertiary ophthalmic center and patients with more severe conditions may have been enrolled and therefore generated selection bias. Second, our center is located in an economically developed area of China, and socioeconomic status might affect QOL as well. Third, there are specific questionnaires for the QOL of children with allergic rhinitis and asthma,40-42 but an AC-specific questionnaire is unavailable.
The findings of our case-control study showed that AC appears to have a negative association with the QOL of both children and their parents, especially in children with VKC/AKC and those with more severe corneal complications. This finding suggests the multifaceted association of AC with QOL; detailed assessment of QOL may be useful to inform chronic condition care for children with AC.
Accepted for Publication: April 8, 2021.
Published Online: June 10, 2021. doi:10.1001/jamaophthalmol.2021.1708
Corresponding Author: Lingyi Liang, MD, PhD, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 7 Jinsui Rd, Guangzhou, Guangdong 510000, China (firstname.lastname@example.org).
Author Contributions: Drs Zhang and Li contributed equally to this work, had full access to all the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Zhang, Li, Liang, Y. Liu.
Acquisition, analysis, or interpretation of data: Zhang, Li, R. Liu, Lao, Fan, Jin, Liang.
Drafting of the manuscript: Zhang, Li, Lao, Liang, Y. Liu.
Critical revision of the manuscript for important intellectual content: Zhang, Li, R. Liu, Fan, Jin, Liang.
Statistical analysis: Zhang, Li, R. Liu, Fan, Jin, Liang.
Obtained funding: Liang.
Administrative, technical, or material support: Lao, Liang.
Supervision: Zhang, Liang, Y. Liu.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by grants 81770892 and 82070922 from the National Natural Science Foundation of China, and grant 2019A1515012012 from the Science Foundation of Guangdong Province.
Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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