Health-related Quality of Life in Children with Vernal Keratoconjunctivitis in Malaysia
Article information
Abstract
Purpose
There has been a lack of data on health-related quality of life (HRQoL) in children with vernal keratoconjunctivitis (VKC) from Southeast Asia. This study evaluated the levels (mean total score and subscales score) of HRQoL, comparing the VKC and normal children groups, and within the VKC severity groups.
Methods
A cross-sectional study was conducted in two tertiary hospitals, specifically the pediatric ophthalmology services at Hospital Selayang and Universiti Sains Malaysia, spanning from 2019 to 2020. Participants aged between 8 and 15 years were categorized into two groups: those diagnosed with VKC and healthy children serving as the control group. Each participant completed the Quality of Life in Children with Vernal Keratoconjunctivitis (QUICK) questionnaire, consisting of 16 questions, divided into two subscales: 12 questions focusing on symptoms and four questions for daily activities.
Results
A total of 240 children took part in the study, with 120 children diagnosed with VKC and another 120 in the control group. The mean age of participants with VKC was 11.21 ± 1.91 years, with a male predominance of 4:1 compared to female. Tearing (98.4%) and itchiness (98.3%) emerged as the most prevalent symptoms affecting HRQoL, while the most challenging activities were outdoor play (36.6%) and participation in recreational water activities (34.2%). The mean total score was significantly higher in the VKC group compared to the control group. Additionally, both the mean total score and all subscale scores were significantly higher in the severe type compared to the mild-moderate type.
Conclusions
VKC significantly reduce the HRQoL among Malaysian children, and the negative impact increases with the disease severity.
Vernal keratoconjunctivitis (VKC) is a recurring chronic inflammation of the eyes with a broad geographical distribution. Its prevalence ranges from 1.2 to 10.6 cases per 10,000 population in Europe [1–4]. VKC is more prevalent in regions with warmer, drier climates, such as the Mediterranean, central and west Africa, the Middle East, Ethiopia, and the Indian subcontinent [5–8]. There is limited data on the prevalence of VKC in Asian countries, including Japan, Thailand, and Singapore [9–11]. The presentation of VKC varies widely across Asia, largely depending on geography and climate [12]. Worsening of VKC in Asia has been reported due to air pollution and Asian dust storms [13,14].
Children diagnosed with VKC often endure recurring symptoms including eye redness, burning discomfort, tearing, ropy discharge, itchiness, and frequent eye rubbing. This condition significantly affects their overall well-being, daily functioning, school attendance, and academic performance [15–17].
Studies conducted in Italy and Northern India have investigated the health-related quality of life (HRQoL) in children with VKC using the Quality of Life in Children with Vernal Keratoconjunctivitis (QUICK) questionnaire [18–23]. This study is significant because it describes the HRQoL in children affected by VKC in tropical climate country, a topic not previously addressed according to PubMed searches. Therefore, our objective was to evaluate the HRQoL in Malaysian children with VKC using the QUICK questionnaire.
Materials and Methods
Ethics statement
Ethical approval for the study was obtained from the Ethical Committee of School of Medical Sciences, Universiti Sains Malaysia (No. USM/JEPEM/18090439) and the Medical Research and Ethics Committee of the Malaysian Ministry of Health (No. NMRR-18-2990-42922(IIR)). Written informed consent was obtained from each parent, and assent was obtained from the recruited participants. The study adhered to the principles outlined in the Declaration of Helsinki for human research.
Study design and population
This comparative cross-sectional study was performed between February 2019 and May 2020, involving children aged 8 to 15 years old with VKC and a control group. The study was carried out at two tertiary referral centers for pediatric ophthalmology services in Malaysia, namely Hospital Selayang (Batu Caves, Malaysia) and Hospital Universiti Sains Malaysia (Kubang Kerian, Malaysia).
The recruitment of the VKC and control group patients relied on the specific eligibility criteria for sampling. VKC diagnosis was established through a combination of the patient’s clinical history, previous diagnoses, and objective examinations [18,24,25]. For the control group, participants were selected from children without any existing ocular issues. Previous ocular history, including intraocular trauma, surgery, complications of ocular disease, secondary glaucoma was carefully excluded from the study. Additionally, exclusion criteria encompassed patient and parents who declined participation in the test and those with limited proficiency in English.
Outcome measures
Demographic and clinical data including age, ethnicity, sex, education level, onset of symptoms, current symptoms, family history, history of comorbidities, allergic history, duration of diagnosis, and current treatment regime were meticulously recorded. A comprehensive ocular examination was performed, which encompassed baseline visual acuity assessment, measurement of intraocular pressure, and examination of both the anterior and posterior segments of the eye. Participants diagnosed with VKC were categorized into mild, moderate, and severe based on their clinical assessment [18,24,25].
All participants were administered the QUICK questionnaire and provided with clear explanations of its content in simple language. Children were asked to complete the QUICK questionnaire independently during enrolment, in a private room, while accompanying parents waited in a separate area. Any participants encountering difficulty understanding the question were encouraged to seek clarification. The participants took approximately 10 to 15 minutes to complete all questionnaire items. The quantification of quality of life in children with VKC was assessed using the QUICK questionnaire [26].
The QUICK questionnaire comprises 16 questions divided into two domains: 12 questions focusing on symptoms that impact quality of life and four questions related to daily activities. For symptoms associated with severe allergic conjunctivitis and daily physical activities (such as swimming, outdoors play, participation in school sports, and socializing with friends), each question utilizes a Likert-type response scale ranging from 1 (never), 2 (sometimes), and 3 (always).
Statistical analysis
Statistical analysis was conducted using IBM SPSS ver. 26.0 (IBM Corp.). Categorical demographic and clinical data were analyzed using descriptive statistics via frequency tests. The independence t-test was utilized to compare mean total and subscale scores between the two groups of the QUICK questionnaire. Additionally, a one-way analysis of variance was employed to determine the significance of differences among the mean total and subscale scores across the three subgroups of children with VKC patients. Quantitative data were presented as mean (standard deviation). A significance threshold of p < 0.05 was considered for all tests.
Results
A total of 240 participants were enrolled in the study, evenly divided into VKC and control groups, each comprising 120 participants (Table 1). The mean age of VKC participants 11.21 ± 1.91 years. Among them, 75 participants (62.5%) fell within the age ranged 8 to 12 years. Male sex predominated in both groups. The majority of participants identified as Malays and were attending primary schools. Notably, a significant proportion of VKC participants had a positive family history of atopy, with 22 (18.3%) reporting bronchial asthma and 40 (33.3%) indicating allergic rhinitis. Furthermore, allergic history was present in 37 participants (30.8%) within the VKC group.
Demographic characteristics of children with VKC compared to the control group (n = 240)
Table 2 describes the participants with VKC categorized according to severity. A total of 120 participants were classified into three severity groups, each comprising 40 participants. The onset of symptoms and presentation primarily occurred between 6 to 12 months in cases of mild to moderate severity, while in severe cases, the majority (80%) were diagnosed after 1 year of symptom onset. All participants in the mild group exhibited a conjunctival type of VKC, whereas those in moderate to severe groups presented with a mixed form of the disease involving both the limbal and conjunctival areas. Notably, 14 participants (35.0%) in the severe group presented with shield ulcers. Of the 120 participants, 92 (76.7%) had visual acuity ranging from 6 / 6 to 6 / 12, with none exhibiting visual acuity poorer than 6 / 60.
Demographic and clinical data of participants diagnosed with VKC (n = 120)
All participants received treatment with topical corticosteroids, mast cell stabilizers, and/or antihistamine eye drops. In the mild group, the predominant treatment regimen (97.5%) consisted of dual therapy, compromising a topical antihistamine and mast cell stabilizer; specifically topical olopatadine 0.1%. Conversely, in the severe group, all children were administered triple therapy, which included a combination of topical corticosteroid and olopatadine 0.1%. Supratarsal corticosteroid injections were employed in eight participants with moderate to severe type nonresponsive disease, none of whom experienced post-treatment complications such as glaucoma or other adverse effects.
The QUICK symptoms domain highlighted that the most impactful symptoms affecting HRQoL among children with VKC were watery eyes (98.4%) and itchiness (98.3%). Conversely, most participants did not report difficulties staying in air-conditioned rooms. Regarding daily activities, the primary concerns were outdoor activities (36.6%) and recreational water activities (34.2%) (Fig. 1A, 1B).
The proportion of participants (A) reporting symptoms and (B) engaging in daily activities.
In the severe group, all participants experienced symptoms including photophobia, tearing, itchiness, redness, and blurred vision, with playing outdoors being the most troublesome activity for 55% of them (Fig. 2A, 2B). Statistically significant differences were observed in the mean subscale and total scores between the VKC and control groups (p < 0.05), as well as among the subgroups of VKC severity (mild, moderate, and severe; p < 0.001). Detailed data are presented in Tables 3–5.
Participants in the vernal keratoconjunctivitis severity group (A) reporting symptoms and (B) engaging in daily activities.
Comparison of mean total and mean subscale scores between children with VKC and the control group
Comparison of mean total score and mean subscale score between children with mild, moderate, and severe VKC
Multiple comparison of mean total score and mean subscale score between children with mild, moderate, and severe VKC
Discussion
Recently, there has been increasing emphasis on HRQoL as it provides valuable insights for healthcare professionals into the impact of a patient’s health condition. In a study by Mikhail et al. [27], various HRQoL questionnaires for assessing ocular allergy were discussed, and two questionnaires were highlighted for assessing HRQoL in VKC: the QUICK questionnaire and the Eye Allergy Patient Impact Questionnaire (EAPIQ). In our study, we opted for the QUICK questionnaire. This tool, developed in Italy specifically for children, features targeted questions designed to be quick and simple for completion within a clinical setting when evaluating HRQoL [26]. On the other hand, the EAPIQ, derived from the mini Rhinoconjunctivitis Quality of Life questionnaire, which is commonly used in research on allergic rhinitis QoL [28], caters to various types of ocular allergy and is tailored for adult respondents. Limited studies have explored HRQoL in VKC globally, particularly in regions with hot climates such as Australia, Italy, India, and China [19,23,29,30].
In this study, the mean age of participants with VKC was 11.21 ± 1.91 years. VKC is typically regarded as a childhood disorder, often resolving by puberty. However, intriguingly, we noted that approximately 37.5% of participants fell within the age range of 13 to 15 years. Saboo et al. [31] reported a mean age of 12 years, with around 12% of cases presenting in individuals older than 20 years, while Leonardi et al. [32] found this occurrence to be only 8%. A notable sex difference was observed in our study, with a male to female ratio of 4:1, accounting for 96 male and 24 female participants. Similar male predominance has been reported in most other published series [33,34]. However, research conducted by Kansakar [35] showed a lower and almost equal ratio among individuals older than 20 years. The male predominance observed in most studies may be attributed to hormonal changes, particularly circulating gonadocorticoids during prepuberty [36]. Additionally, approximately 30.8% of participants in our study had a history suggestive of allergic associations. These findings are consistent with other studies by Leonardi et al. [32] and Nagpal et al. [37], reporting associations of atopy in VKC at rates of 28.6% and 30%, respectively. Such congruent results underline the significance of atopy history in understanding exacerbations in VKC patients.
Our study found that 15% of participants presented with mega cobblestone papillae, while 35% were associated with shield ulcers in the severe group. Importantly, none of the subjects exhibited visual acuity poorer than 6 / 60. The association of mega cobblestone papillae rubbing on the corneal surface may induce multiple punctate erosions, which can later coalesce to form shield ulcers. If left untreated or inadequately managed, a plaque containing fibrin and mucus may form on this epithelial defect, hindering re-epithelialization of the shield ulcer and leading to poor visual outcomes. Bonini et al. [38] reported that out of 195 VKC patients, 16.4% exhibited cobblestone papillae, a finding similar to our study. However, the incidence of shield ulcers was reported to be between 3% to 11%, with subsequent permanent reduction in visual acuity occurring in 6% of cases [34]. This discrepancy could be attributed to variations in disease severity, genetic backgrounds, environmental conditions, and early-stage disease management. Nonetheless, most VKC patients have a favorable visual prognosis. We encountered a local case report of a patient with a shield ulcer presenting with moderate visual acuity of 6 / 24, whose vision improved to 6 / 9 following 2 weeks of surgical debridement for corneal scarring [39].
The mean subscale scores for symptoms and daily activities were higher in VKC patients compared to the control group, indicating a poorer quality of life associated with VKC. Moreover, the significant difference observed in the mean total score between children with VKC and the control group (p < 0.001) further highlights the diminished quality of life in VKC patients. A similar finding was reported in a published article by Zhang et al. [30], which evaluated the association between allergic conjunctivitis and HRQoL in children and their parents using the Pediatric Quality of Life Inventory (PedsQL). The study revealed that median total PedsQL scores were significantly reduced in children with allergic conjunctivitis. However, a study on the effectiveness of antiallergic eye drops demonstrated improvement in HRQoL within a 3-month interval of starting the medication, as evidenced by a decrease in the mean total score response on the QUICK questionnaire [19].
Participants diagnosed with severe VKC exhibited higher mean subscale scores in both symptoms and daily activities compared to those with mild-moderate VKC. This finding suggests that individuals with severe VKC experience a poorer quality of life than those with milder forms of the disease. Moreover, the mean total score in the VKC severity groups revealed a higher score in the severe VKC group (28.85 ± 2.45), followed by the moderate group (26.75 + 3.51), with statistically significant differences (p < 0.01). Notably, individuals with mild VKC generally reported a better quality of life compared to those with moderate to severe disease.
These findings align with those of Leonardi et al. [32], who concluded in their study on VKC-like disease in adults that patients with moderate to severe ocular symptoms experience significant interference with their quality of life. Moreover, individuals experiencing intense ocular discomfort may face challenges in participating in various lifestyle activities.
The QUICK symptoms subscale analysis from our study highlighted common symptoms impacting HRQoL, including tearing (98.4%), itchiness (98.3%), redness (94.2%), and burning sensation (86.7%). These findings closely align with those reported by Sacchetti et al. [26], who found that itching (93%), burning sensation (90%), and redness (90%) were among the most troublesome symptoms experienced by VKC patients. Both studies identified similar limitations in the QUICK daily activities subscale, with swimming pools and outdoor activities being major concerns.
Additionally, our study revealed common symptoms affecting the severe VKC group, including photophobia, tearing, itchiness, redness, and blurred vision, while the most troublesome daily activity was playing outdoors (55%). These results are consistent with those reported by Nebbioso et al. [40], who identified photophobia as the most frequent ocular symptom in severe VKC, followed by tearing, foreign body sensation, itching, and conjunctival hyperemia.
Furthermore, numerous studies have highlighted a detrimental effect on school performance and attendance in school-age children diagnosed with VKC [15,17]. Remarkably, none of the participants in our study had dropped out of school, consistent with findings from De Smedt et al. [17], who also noted that repeating a school year or dropping out of school was uncommon among children with VKC.
This study has its limitations. Our data showed significant differences between the two groups in terms of age, sex, race, and education level (p < 0.05). Ideally, these variables should be comparable between the groups. However, we managed to recruit a large number of participants for the control group.
In conclusion, our study showed the significant negative impact on the symptoms and daily activities based on QUICK questionnaire in Malaysian children with VKC. Understanding the disease impact is crucial to improve the treatment strategy and QoL. These can help the clinicians to understand the patient own perceptions and experiences.
Acknowledgements
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Notes
Conflicts of Interest
None.
Funding
None.