Clinical manifestations and vision-related quality of life in pediatric uveitis

doi:10.21203/rs.3.rs-1873564/v1

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Clinical manifestations and vision-related quality of life in pediatric uveitis

https://doi.org/10.21203/rs.3.rs-1873564/v1

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Background

To analyze clinical manifestations, visual ability and quality of life in pediatric uveitis and to explore factors affecting visual ability and quality of life.

Methods

This cross-sectional study included 40 patients with pediatric uveitis in the database of Ophthalmology of Peking University First Hospital. All patients completed Cardiff visual ability questionnaire for children (CVAQC) and pediatric quality of life inventory measurement models (PedsQL4.0).

Results

A total of 40 cases (68 eyes) with pediatric uveitis were included in this study. Better visual acuity in better eye was predictive of a lower score of CVAQC, education and distance vision. Better visual acuity in worse eye was predictive of a lower score of CVAQC and distance vision. Better scores of CVAQC was predictive of a lower score of PedsQL4.0, physical health, psychosocial health and school functioning.

Conclusions

Health-related quality of life is related with vision ability in pediatric uveitis.

Pediatric uveitis

Clinical manifestations

Visual ability

Quality of life

Pediatric uveitis is defined as uveitis which attacked under the age of 16 years. .Incidence of pediatric uveitis is fairly low, which accounts for 5%-10% of all cases of uveitis¹. The causes of pediatric uveitis are divided into infectious and noninfectious etiologies. The common infectious causes include toxoplasma, syphilis, tuberculosis, herpes virus, etc. ². Juvenile idiopathic arthritis (JIA) is the most common cause in noninfectious etiologies of pediatric uveitis³. According to the literature, it is usually difficult for doctors to diagnose clearly at early course of pediatric uveitis. A part of patients may relapse frequently, which usually leads to low vision and quality of life.

This work aims to investigate the demographic characteristics, clinical patterns, visual ability and quality of life of pediatric uveitis patients presenting to the clinic at Peking University First hospital in order to discuss relevant factors of quality of life in pediatric uveitis patients.

This cross-sectional study of 40 patients with pediatric uveitis was conducted between at the Uveitis

Clinic of Peking University First Hospital, Beijing, China. All patients’ data were collected by standard procedure, including age, gender, laterality of involvement, ocular symptoms, systemic history, treatment and scale scores. Complete ophthalmology examination was performed by uveitis ophthalmologist in all patients, including best-corrected Snellen visual acuity, slit-lamp microscopy, intraocular pressure, dilated completely fundus examination and optical coherence tomography.

All patients were classified anatomically according to the International Uveitis Study Group system as having anterior uveitis, intermediate uveitis, posterior uveitis, or panuveitis⁴. The most common complications of pediatric uveitis included posterior synechiae, glaucoma/ocular hypertension, cataracts, macular edema and band keratopathy. “Posterior synechiae” were defined as adhesions between the iris and lens capsule or large pigment clumps on the anterior lens capsule consistent with past adhesions. “Glaucoma/ocular hypertension” were defined as a previous diagnosis of glaucoma/ocular hypertension; prior glaucoma/ocular hypertension surgery; intraocular pressure measurements higher than 21 mm Hg at any visit; visual field or optic disk changes typical of those seen with glaucomatous optic nerve damage; Patients were defined to have “cataracts” if records identified them as having 1 or more nuclear or cortical opacity or any posterior subcapsular lens opacities. “Macular edema” was considered by either OCT or fluorescein angiography. “Band keratopathy” were identified as calcification in the Descent membrane in patient’s cornea⁵. Patients were classified by the course of disease as acute(less than 3 months), chronic (more than 3 months), and recurrent course (relapsed after 3-month treatment-free withdrawal period).

We used the Cardiff Visual Ability Questionnaire for Children (CVAQC) to form a unidimensional scale for the assessment of the visual ability in children and young people with eye diseases. Designed to be completed by the child, it consists of 25 questions with answers selected on a four-point scale covering education, near and distance vision, getting around, social interaction, leisure, and sports. Huang J, Khadka J, Gao R, et al translated CVAQC into Mandarin using a standard protocol. The CVAQC-CN is a psychometrically robust and valid instrument to measure visual ability in children with visual impairment in China⁶. Lower score of CVAQC means better visual ability. To measure health-related quality of life (HRQOL) in children and adolescents, we used the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0). The PedsQL 4.0 Generic Core Scales consist of 23 items applicable for healthy school and community populations, as well as pediatric populations with acute and chronic health conditions. Lower score of PedsQL4.0 means lower quality of life.

Data were coded and entered using the statistical package SPSS (Statistical Package for the Social Sciences) version 23. We reported means and standard deviations for normally distributed data as _x±s or median and interquartile range (IQR) for data non normally distributed data as M (P₂₅, P₇₅). For comparing categorical data, Chi-square (χ2) test was used. Comparisons between quantitative variables were done by the non-parametric Mann-Whitney tests. We performed Spearman correlation test to analyze the relevance among variables, P-values less than 0.05 were considered as statistically significant.

This study included 68 eyes of 40 patients (18 male and 22 female) with pediatric uveitis. Demographic and disease characteristics of patients collected in our study are summarized in Table 1. Mean age of onset was 10.025 ± 3.252 years. Median follow-up time was 1 year (range: 0.5–5 years). The ratio of unilateral uveitis to bilateral uveitis was 1:2.33. There were juvenile idiopathic arthritis (JIA) in 4 patients, tubulointerstitial nephritis and uveitis syndrome (TINU) in 4 patients, 1 patient in sarcoidosis, 1 patient in Sjogren's syndrome, 1patient in Behçet disease and 1 patient in measles. According to anatomical classification, the most common type was panuveitis (60%), followed by anterior uveitis(32.5%), then intermediate uveitis(5%), and posterior uveitis(2.5%) was least. Ocular complications were developed in 29 patients (72.5%). The most common complications were glaucoma/ocular hypertension (15 patients), posterior synechiae (13 patients), cataracts (12 patients) and band keratopathy (9 patients). Other complications (macular edema, papilledema, ciliary body edema and strabismus) were also observed in the study. 17 patients (42.5%) were observed to undergo the acute course of disease, while 7 patients (17.5%) suffered more than 3 months of uveitis. 21 patients (52.5%) relapsed within 3-month drug withdrawal. All patients received therapy of corticosteroids by eye drops. Posterior sub-tenon triamcinolone acetonide injection was used in 4 patients. 2 patients received intravitreous injection of Ozurdex. Immunomodulatory agents were also used in 17 patients. 9 patients used one kind of immunomodulatory agent and 8 patients used two kinds of immunomodulatory agent to control inflammation. Adalimumab was also used in 2 patients.

We also compared the difference of therapeutic strategies in this study with Chi-squared test which was shown in Table.2. Compared to patients with topical medical therapy, patients who received systematic medical therapy were significantly more frequent to suffer from ocular complications, especially in patients with glaucoma/ocular hypertension (P = 0.002) and posterior synechiae (P = 0.045). Anterior chamber inflammation in all patients was relieved after one-week treatment with topical glucocorticoid eye drops. However, uveitis in most of patients with systematic medical therapy showed a recurrent course after drug withdrawal except 3 patients (11.1%).

We enrolled 40 patients in this study and excluded 2 data sets of patients who did not completed the whole questionnaire. The median total score of CVAQC and PedsQL4.0 was − 4.853(IQR − 5.020 to -4.853) and 96.74 (IQR 90.22 to 100.00).

All patients were divided into several groups by gender, age of onset, anatomy, systemic diseases, course of disease, complications and unilateral/bilateral diseases to compare the difference in scores of scales. Physical health scores of PedsQL4.0 were significantly lower in patients with onset less than the age of 10 than patients with onset more than the age of 10 (P = 0.007). Scores in sports of CVAQC, total scores of PedsQL4.0 and physical health scores of PedsQL4.0 were statistically lower in patients with systematic diseases than patients without systematic diseases (P = 0.030, P = 0.018, P = 0.003). Total scores of CVAQC, scores in near vision of CVAQC, total scores of PedsQL4.0, psychosocial health and school functioning scores of PedsQL4.0 were statistically lower in patients with panuveitis than other patients (P = 0.022, P = 0.010, P = 0.049, P = 0.020, P = 0.025). Total scores of CVAQC and PedsQL4.0 were lower in patients with chronic and recurrent course than patients with acute course (P = 0.018, P = 0.024). Scores of CVAQC and PedsQL4.0 were not significantly associated with gender of patients. Scores of CVAQC and PedsQL4.0 were lower in patients with ocular complications than patients without ocular complications (P > 0.05, data not presented). Scores of CVAQC and PedsQL4.0 were lower in patients suffered from unilateral diseases than patients suffered from bilateral diseases (P > 0.05, data not presented).

BCVA in better eye was statistically associated with total scores of CVAQC, subgroups scores in education and distance vision of CVAQC, with lower BCVA in better eye associated with higher scores of CVAQC (P = 0.033, P = 0.048, P = 0.004). BCVA in worse eye was statistically associated with total scores of CVAQC and subgroups scores in distance vision of CVAQC, with lower BCVA in better eye associated with higher scores of CVAQC (P = 0.025, P = 0.037) (Table.3). Total scores of CVAQC was statistically associated with total scores of PedsQL4.0, scores in physical health, psychosocial health and school functioning of PedsQL4.0, with lower scores of CVAQC associated with higher scores of PedsQL4.0 (P < 0.001, P = 0.006, P = 0.002, P = 0.001) (Table.4).

In this study, the ratio of male to female of pediatric uveitis was 1:1.22, which is same as the published report (1:1–1:1.6)^7–9. 70% of all patients enrolled in the study suffered from bilateral uveitis. That was similar with the ratio which reported by other study before^{5, 9}. Most of cases were panuveitis (60%) and the proportion was higher than that in prior studies, which could be due to the concentration of intractable panuveitis from different parts of the country. As mentioned in the literature review, 5.1%-81.5% of patients was caused by JIA, which was the main etiology of non-infectious pediatric uveitis². Other common causes, including TINU, sarcoidosis, Sjogren's syndrome and Behçet disease, were same as that reported by previous studies. The follow-up time in this study was ranged from 0.1 to 5 years. Ocular complications were observed in 72.5% of all patients, including glaucoma/ocular hypertension, posterior synechiae, cataracts, band keratopathy and so on. In Rosenberg’s study, there were 34% patients with ocular complications at an initial visit of clinic. The proportion of patients with complication raised to 61.6% after 3 months, and one or more types of ocular complications were occurred in 86.3% patients after 3 years⁵. A study in Europe reviewed 653 cases of adult uveitis with a 3–59 months follow-up time, and there were 43.5% patients occurred ocular complications in all patients. The proportion of ocular complication in uveitis was much lower in adults than that in children and adolescents¹⁰. Sijssens and colleagues found that the content of 12 inflammation-related cytokines (Th1, IL-2, IL-4, IL-10, IL-12, IL-18, TNF-α, etc.) in aqueous fluid was higher in pediatric patients than the content in adult patients¹¹. This result may explain the reason for the high incidence of ocular complications in pediatric uveitis.

That is still a challenge for the treatment of non-infectious pediatric uveitis. All patients received therapy of corticosteroids by eye drops. Immunomodulatory agents were used in 42.5% patients. 22.5% patients used one kind of immunomodulatory agent and 20% patients used two kinds of immunomodulatory agent to control inflammation. An American study reviewed 323 cases of pediatric uveitis. Only one patient with unilateral anterior uveitis was cured by topical treatment. 2.52 ± 1.46 kinds of systematic drugs, which showed the difficulty in treatment of pediatric uveitis¹². Biologic agents (adalimumab) were applied in 5% patients in this study. This ratio was significantly less than that in France (41%)¹³. In our opinion, it was partly due to the medical insurance policy in China, which didn’t pay for adalimumab in treatment of uveitis. What’s more, parents of patients knew quite little about the application of biologic agents. We hope that biologic agents could be applied more widely in the future treatment in China.

Combined results of this study and previous studies, we can draw several conclusions. The pathogenesis of pediatric uveitis is concealed. Patients usually suffer from systematic diseases and go through chronic or recurrent course of disease. Ocular complications occur early and badly. Pediatric uveitis remains mostly intractable to existing treatments. Systematic treatment, including glucocorticoid, immunomodulatory agent and biologic agent, is often used for a long course. Unlike adults, children and adolescents have a lot of uncertainty in physical, mental and social function during their growth and development. So it is significant to evaluate patients’ visual ability and quality of life influenced by pediatric uveitis.

As biomedical domain develops, there is a tendency to take patients' subjective feeling into consideration when evaluated the medical prognosis of diseases. Study of scales has become a hot pot in recent years, which was applied in evaluating the effects of disease on physiological and psychological function. For the past few years, overseas studies have achieved a lot of results in vision-related scales in adults^{14, 15}. Domestic research results have concentrated on introduction of mature scales which recognized by most foreign researchers⁶. With the consideration of difference in lifestyle and social role between children and adults, those reported results in adults could not be copied in children. So it is necessary to design measuring tools especially for children to evaluate the subjective sense. PedsQL4.0 was developed as a generic instrument which was used in clinical trials. It was translated into Mandarin and was applied in studies of various kinds of children diseases. In this study, the median total scores of PedsQL4.0 was 96.74 (90.22, 100.00), which is higher than total scores of glaucoma and cataract in foreign studies^{16, 17}. On one hand, patients’ BCVA of the better eye was good enough to perform daily activities in this study. On the other hand, due to implicit culture Chinese were not used to describe their situation with absolute and extreme terms, like “very difficult”. School functioning was affected mostly in all subgroups. Many patients chose the option “be absent through illness”. Patients with onset less than the age of 10 reported low scores in physical health. This result also agrees with previous research¹⁷. Panuveitis patients, patients with systematic diseases, patients with chronic and recurrent course had lower scores of PedQL4.0, which means worse quality of life. These conclusions also agree with the common sense.

Visual development in childhood is important in studying, working, socializing and other aspects for children. Impaired vision in childhood could cause worse outcome than impaired vision as adults. To evaluate functional visual ability of our patients, CVAQC was used in this study. In this study, the overall visual ability of patients with pediatric uveitis decreases significantly. The most prominent change is in near vision. Panuveitis, chronic and recurrent course predicts worse visual ability. BCVA of better eye is positively associated with overall visual ability, education and distance vision function. BCVA of worse eye is positively associated with overall visual ability and distance vision function. These results are also consistent with that of children with glaucoma¹⁸. That shows the meaning of early treatment and saving vision in time to conserve visual ability. Total scores of CVAQC was statistically associated with total scores of PedsQL4.0, scores in physical health, psychosocial health and school functioning of PedsQL4.0. It illustrates that health-related quality of life is intensively related with vision ability in pediatric uveitis.

Within the limits of the study design, such as enrolling participants at a single site and with small sample size, our findings can be generalized to other children from hospitals at all levels. More research is needed to measure the vision-related quality of life in pediatric uveitis.

Cardiff visual ability questionnaire for children (CVAQC)

Pediatric quality of life inventory measurement models (PedsQL4.0)

Juvenile idiopathic arthritis (JIA)

Health-related quality of life (HRQOL)

Interquartile range (IQR)

Tubulointerstitial nephritis and uveitis syndrome (TINU)

Ethics approval and consent to participate

This study followed the tenets of the Declaration of Helsinki and conducted with approval from the Ethics Committee of Peking University First Hospital. A written informed consent was obtained from each participant and his (or her) parent.

Consent for publication

The written consent for publication of this article and the accompanying tables has been obtained from the participant.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Competing interests

The authors declare that they have no competing interests.

Funding

No funding was received.

Author information

Affiliations

Department of Ophthalmology, Peking University First Hospital, Beijing, 100034, China

Yiran Li, Liu Yang

Authors Contributions

YL: Writing the manuscript, collection of data, submission.

LY: Reviewing the manuscript, critical review of the manuscript.

All authors have read and approved the manuscript.

Corresponding author

Correspondence to Liu Yang

Acknowledgements

Not applicable.

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Table.1 Demographic and clinical characteristics of patients enrolled in this study.

Male/Female	1:1.22
Unilateral / Bilateral	1:2.33
Etiology
Juvenile idiopathic arthritis (JIA)	4(10.0)
Tubulointerstitial nephritis and uveitis syndrome (TINU)	4(10.0)
Sarcoidosis	1(2.5)
Sjogren's syndrome	1(2.5)
Behçet disease	1(2.5)
Measles	1(2.5)
Anatomical classification
Anterior	13(32.5)*
Intermediate	2(5.0)
Posterior	1(2.5)
Panuveitis	24(60.0)
Complications
Posterior synechiae	13(32.5)
Glaucoma/ocular hypertension	15(37.5)
Cataracts	12(30.0)
Macular edema	1(2.5)
Band keratopathy	9(22.5)
Papilledema	1(2.5)
Ciliary body edema	1(2.5)
Strabismus	1(2.5)
Course of disease
Acute	12(40.0)
Chronic	7(17.5)
Recurrent	21(52.5)
Therapeutic strategies
Corticosteroid	40(100)
Eye drops	40(100)
Posterior sub-tenon triamcinolone acetonide	4(10.0)
Oral administration	26(65.0)
Ozurdex	2(5.0)
Immunomoduratory agents	17(42.5)
One kind	9(22.5)
Two kinds	8(20.0)
Adalimumab	2(5.0)

* Percentages.

Table.2 Comparison of topical medical therapy and systemic medical therapy in pediatric uveitis

	Only topical medical therapy(n=13)	Systemic medical therapy(n=27)	c²	P
With systemic diseases	4(30.8%)	11(40.7%)	0.372	0.542
complicated cataract	2(15.4%)	10(37.0%)	1.959	0.162
glaucoma/ocular hypertension	2(15.4%)	13(48.1%)	4.019	0.045*
posterior synechiae	0(0.0)	13(48.1%)	9.273	0.002**
band keratopathy	1(7.7%)	8(29.6%)	2.422	0.120

P value was analyzed by Chi-squared test. *P<0.05，**P<0.01.

Table.3 Correlation of BCVA and scores of scales

Items	Correlation coefficient of BVCA in better eye	P	Correlation coefficient of BVCA in better eye	P
Total score of CVAQC	-0.346	0.033*	-0.364	0.025*
Education	-0.323	0.048*	-0.120	0.473
Near vision	-0.297	0.236	-0.340	0.037*
Distance vision	-0.459	0.004**	-0.197	0.237
Getting around	0.224	0.177	0.075	0.652
Social interaction	0.054	0.747	-0.015	0.928
Entertainment	-0.180	0.287	0.203	0.229
Sports	-0.306	0.062	-0.149	0.371
Total score of PedsQL4.0	0.309	0.059	0.228	0.168
Physical Health	0.247	0.135	0.125	0.455
Psychosocial Health	0.266	0.106	0.257	0.120
Emotional Functioning	0.038	0.820	0.158	0.344
Social Functioning	-	-	-	-
School Functioning	0.307	0.061	0.240	0.147

P value was analyzed by Spearman correlation test.*P<0.05，**P<0.01.

Table.4 Correlation of total scores of CVAQC and scores of subgroups scores of PedsQL4.0

Items	Correlation coefficient of CVAQC	P
Total score of PedsQL4.0	-0.539	<0.001**
Physical Health	-0.434	0.006**
Psychosocial Health	-0.493	0.002**
Emotional Functioning	-0.205	0.217
Social Functioning	-	-
School Functioning	-0.503	0.001**

P value was analyzed by Spearman correlation test. **P<0.01.

No competing interests reported.

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Clinical manifestations and vision-related quality of life in pediatric uveitis

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Abstract

Background

Methods

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Conclusions

Introduction

Material And Methods

Results

Disscusion

Abbreviations

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References

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