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Increased Incidence of Mental Disorders in Children with Cataract: Findings from a Population-based Study

Open AccessPublished:October 11, 2021DOI:https://doi.org/10.1016/j.ajo.2021.09.034

      PURPOSE

      To examine the incidence of mental disorders in children with cataract compared with children without cataract.

      DESIGN

      Nationwide cohort study based on entries in comprehensive national databases.

      METHODS

      The incidence of mental disorders in children born between 2000 and 2017 diagnosed with cataract before 10 years of age (n = 485) was compared with sex- and age-matched controls (n = 4358). Analyses were corrected to somatic disease in the child and parental socioeconomic status and psychiatric morbidity. The study was conducted as 2 university hospitals in Denmark managing children 6 years of age our younger with cataract.

      RESULTS

      The incidence of mental disorders was nearly doubled in children with cataract compared with controls (odds ratio [OR], 1.83; 95% CI, 1.28–3.63). The risk of anxiety disorders was quadrupled (OR, 4.10; 95% CI, 1.90–8.84) and the risk of developmental delay was doubled (OR, 2.66; 95% CI, 1.45–4.90). The risk of mental disorders was significantly higher in children diagnosed with cataract in the first 3 years of life compared with controls (OR, 2.36; 95% CI, 1.53–3.64), whereas those diagnosed with cataract later in childhood did not have an increased risk (OR, 1.24; 95% CI, 0.66–2.30).

      CONCLUSIONS

      The risk of mental disorders, in particular anxiety and neurodevelopmental delay, is markedly increased in children with cataract and even more so in those diagnosed within the first 3 years of life. Psychiatric screening instruments may be integrated in the management of these children.
      Clinical and research evidence point to an increased risk of mental health problems and disorders in children and adolescents suffering from chronic diseases.
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      Thus, attention deficit/hyperactivity disorders and autism spectrum disorders (ASD) are more frequent among children with cerebral palsy,
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      and anxiety and depression have been found in 1 of 4 children with epilepsy.
      • LaGrant B
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      Depression and anxiety in children with epilepsy and other chronic health conditions: national estimates of prevalence and risk factors.
      In children with diabetes type I, an increased risk of anxiety, mood disorders, and eating disorders have been shown in the years after disease onset.
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      Increasing risk of psychiatric morbidity after childhood onset type 1 diabetes: a population-based cohort study.
      Childhood cataract is a significant cause of visual disability in infancy and early childhood, affecting approximately 200,000 children worldwide.
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      Visually disturbing cataracts can be removed by surgery,
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      Most cases of childhood cataract occur in early childhood,
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      which is also the period of onset of several childhood mental disorders, in particular neurodevelopmental disorders.
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      Children with cataract are more likely to come from a socioeconomically disadvantaged background,
      • Al-Bakri M
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      • Kessel L.
      Socio-economic status in families affected by childhood cataract.
      which may further increase the risk of pediatric child mental disorders.
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      • Hysing M.
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      ,
      • Reiss F.
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      Two questionnaire studies based on parental reporting found a higher risk of conduct problems, learning problems, psychosomatic problems, impulsiveness/hyperactivity, and anxiety problems in children with cataract compared with children with normal vision
      • Lin Z-L
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      Increased prevalence of parent ratings of ADHD symptoms among children with bilateral congenital cataracts.
      and a lower level of psychosocial health in children with cataract, which was similar to the psychosocial health level of children with other severe somatic diseases like rheumatological disease and cancers.
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      The health-related quality of life of children with congenital cataract: findings of the British Congenital Cataract Study.
      The aim of the present study was to examine the risk of mental disorders in children with childhood cataract compared with children without cataract using Danish population registries and taking into account potential confounders such as parental socioeconomic status, family psychiatric load, and the children's somatic comorbidity.

      METHODS

       STUDY POPULATION

      We included patients born from January 1, 2000, to December 31, 2017, who were diagnosed with cataract before age 10 years at 1 of the 2 hospitals that manage all children with cataract in Denmark: Rigshospitalet, Copenhagen, and Aarhus University Hospital, Aarhus (see Figure 1). In Denmark, each person has a unique identification number (CPR number). The CPR number is used in national administrative registries which makes it possible to link data from individuals accurately between registries. In addition, children are linked to their parents by the CPR number.
      Figure 1
      Figure 1Flow chart showing inclusion and exclusion of the study population.

       CONTROL POPULATION

      For each child with cataract, a sample of 10 children without cataract matched by age, sex, and municipality were sampled from the general Danish population by Statistics Denmark.

      Statistics Denmark. Accessed January 4, 2021. www.dst.dk/en#.

       DATA FROM NATIONAL POPULATION REGISTRIES

      We used data from the following national registries: National Patient Registry (NPR), which contains information about diagnostic and procedural International Classification of Diseases, 10th edition (ICD-10) codes on all contacts to public hospitals, as in- or out-patient and including emergency settings. The Population Registry was used to access information about child sex, geographical birth origin, and parental socioeconomic status. Information regarding parental work status was extracted from the AKM registry (work classification module). Parental civil status was obtained from BEF registry (population registry) and information on parental income was obtained from the income registry. In addition, we extracted information on parental mental disorders from the NPR (Supplementary Table 1). Any variables with fewer than 5 observations cannot be tabulated according to the policy of Statistics Denmark.

       MENTAL DISORDERS

      The presence and type of mental disorders diagnosed during the first 10 years of life were assessed using the ICD-10 diagnostic codes (F00–F99 and R41.8, R62.0, R62.9) listed in the NPR. The latter codes for unspecific developmental delays are commonly used among Danish pediatricians and child psychiatrists to categorize unspecific developmental delay in younger children who often have more subtle and unspecific symptoms of developmental delays compared with older children.
      • Koch S V
      • Andersson M
      • Hvelplund C
      • Skovgaard AM.
      Mental disorders in referred 0-3-year-old children: a population-based study of incidence, comorbidity and perinatal risk factors.
      In accordance with the latest version of the international classification schemes
      • Thapar A
      • Cooper M
      • Rutter M.
      Neurodevelopmental disorders.
      ,
      • Thapar A RM
      Neurodevelopmental disorders.
      and recent research in the field,
      • Dybdal D
      • Tolstrup JS
      • Sildorf SM
      • et al.
      Increasing risk of psychiatric morbidity after childhood onset type 1 diabetes: a population-based cohort study.
      ,
      • Sildorf SM
      • Breinegaard N
      • Lindkvist EB
      • et al.
      Poor metabolic control in children and adolescents with type 1 diabetes and psychiatric comorbidity.
      we grouped the mental disorders as neurodevelopmental and other mental disorders:

       Neurodevelopmental disorders

      Neurodevelopmental disorders included intellectual disability (F70–F79), specific developmental disorders (F80–F83), ASD (F84), unspecified developmental disorders (F88–F89), hyperkinetic disorder (F90), and unspecific developmental delay (R41.8, R62.0, R62.9).

       Other mental disorders

      Other mental disorders included psychoactive substance misuse (F10–F19), psychotic disorders (F20–F29), mood disorders (F30–F39), anxiety, dissociative, stress-related, and somatoform disorders (F40–F48), eating disorders (F50), sleep disorders and medication abuse (F51–59), personality disorders (F60–F69), and other mental or behavioral disorders (F91–F99).
      The term any mental disorders included all the above-mentioned diagnostic codes. Notably, a child could be diagnosed with 2 or more different mental disorders. However, each child could be counted only once in the analysis of overall incidence of any mental disorder. When exploring the risk of specific psychiatric disorders, each child could figure in more than 1 subgroup if they had more than 1 diagnosis, but only once in each category.

       Somatic comorbidities

      Because childhood cataract is often found in association with systemic disease or as part of a syndrome, we subgrouped the cataract population into (1) children with isolated cataract and (2) children with cataract and severe somatic comorbidities (Supplementary Table 2).

       CONFOUNDERS

      Some somatic comorbidities were potential confounders (disease confounders) because either the disease itself or its treatment may increase the risk of cataract as well as mental disorders. This group included interstitial lung disease (J84.9 + J84.8 + J84.1) owing to treatment with high doses of prednisolone,
      • Jobling AI
      • Augusteyn RC.
      What causes steroid cataracts? A review of steroid-induced posterior subcapsular cataracts.
      ,
      • MacKenzie EM
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      • Prior TI
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      The relevance of neuroactive steroids in schizophrenia, depression, and anxiety disorders.
      congenital rubella syndrome (P35.0 + B06.0 + B06.8 + B06.9),
      • Hered RW.
      Pediatric ophthalmology and strabismus, Section 6.
      • Chess S
      • Fernandez P
      • Korn S.
      Behavioral consequences of congenital rubella.
      • Chauhan N
      • Sen MS
      • Jhanda S
      • Grover S.
      Psychiatric manifestations of congenital rubella syndrome: a case report and review of literature.
      congenital cytomegalovirus infection (B25.0 + B25.1 + B25.2 + B25.8 + B25.9 + P35.1),
      • Hered RW.
      Pediatric ophthalmology and strabismus, Section 6.
      ,
      • Gentile I
      • Zappulo E
      • Riccio MP
      • et al.
      Prevalence of congenital cytomegalovirus infection assessed through viral genome detection in dried blood spots in children with autism spectrum disorders.
      degenerative disease of the nervous system (G31 + G31.1 + G31.9)
      • Eddy CM
      • Parkinson EG
      • Rickards HE.
      Changes in mental state and behaviour in Huntington's disease.
      ,
      • Muchowski PJ
      • Ramsden R
      • Nguyen Q
      • et al.
      Noninvasive measurement of protein aggregation by mutant huntingtin fragments or alpha-synuclein in the lens.
      and cancer in the brain or meninges owing to radiation therapy (C70-72.9 + C76.0 + C69),
      • Chodick G
      • Sigurdson AJ
      • Kleinerman RA
      • et al.
      The risk of cataract among survivors of childhood and adolescent cancer: a report from the Childhood Cancer Survivor Study.
      • Willard VW
      • Berlin KS
      • Conklin HM
      • Merchant TE.
      Trajectories of psychosocial and cognitive functioning in pediatric patients with brain tumors treated with radiation therapy.
      • Willard VW
      • Conklin HM
      • Wu S
      • Merchant TE.
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      microcephaly (Q02.9), megalencephaly (Q04.5), Smith-Lemli-Opitz’ syndrome (Q87.1I), trisomy 21 (Q90.0-90.2), Down's syndrome (Q90 + Q90.9), and autosomal trisomies (Q92-92.9). Severe somatic comorbidities in the cataract group are listed in Supplementary Table 2.
      Children with cataract have previously been shown to be more likely to come from socioeconomically disadvantaged families
      • Al-Bakri M
      • Bach-Holm D
      • Larsen DA
      • Siersma V
      • Kessel L.
      Socio-economic status in families affected by childhood cataract.
      and many pediatric mental disorders are more prevalent in families of lower socioeconomic status.
      • Bøe T
      • Sivertsen B
      • Heiervang E
      • Goodman R
      • Lundervold AJ
      • Hysing M.
      Socioeconomic status and child mental health: the role of parental emotional well-being and parenting practices.
      ,
      • Reiss F.
      Socioeconomic inequalities and mental health problems in children and adolescents: a systematic review.
      Hence, in addition to disease confounders, the statistical analyses were also adjusted for the geographical birth location of the child and parental socioeconomic status (income, employment, and civil status). Definition of these variables were described previously in detail
      • Al-Bakri M
      • Bach-Holm D
      • Larsen DA
      • Siersma V
      • Kessel L.
      Socio-economic status in families affected by childhood cataract.
      and are available in (Supplementary Table 3).
      Because parental mental disorders may predispose to child mental disorder,
      • Mattejat F
      • Remschmidt H.
      The children of mentally ill parents.
      we adjusted for any mental disorders diagnosed at hospital (F00–F99) in 1 or both parents.

       STATISTICAL METHODS

      The association between childhood cataract and mental disorders was assessed using odds ratios (OR) with 95% CIs in unadjusted analyses and in conditional logistic regression models, including age at onset of cataract, sex, and the confounders described elsewhere in this article. Adjusted and unadjusted analyses were repeated separately in each of the 2 cataract onset age groups: 0 to 3 years and 4 to 10 years, a test for interaction was added. Statistical analyses were made using the R software package, V.3.4.1 (The R Foundation for Statistical Computing, http://www.r-project.org). The significance level was set at a P value of less than .05.

       APPROVALS

      The study was approved by the Danish Data Protection Agency (RH-2016-336; I-Suite # 05070), and the Danish Patient Safety Authority (3-3013-1935/1/NAAN). According to the Committee on Health Research Ethics in the Capital Region of Denmark, ethical board review was not required (decision number: 16038234). The study followed the tenets of the Helsinki Declaration.

      RESULTS

      We included 485 children (243 boys and 242 girls) with childhood cataract and an age- and sex-matched control group (n = 4,358; 2,177 boys and 2,181 girls) drawn from the background population. Baseline characteristics of the study population are listed in Table 1. No difference in parental mental health was found between the 2 groups. The majority of the children in the cataract group had been operated (n = 282/485 [58.1%]).
      TABLE 1Characteristics of the Study Population.
      Children with CataractChildren without CataractP value
      P value: Likelihood ratio test in a conditional logistic regression.
      (n = 485)(n = 4358)
      Child's birth place, n (%).001
      Significant p-value.
       Denmark428 (88.2)4,030 (92.5)
       Outside Denmark57 (11.8)328 (7.5)
      Disease confounders
      Severe somatic diseases: congenital syndrome: microcephaly, megalencephaly, Smith–Lemi–Opitz' syndrome, trisomy 21, Down's syndrome, partial autosomal trisomy, cytomegalovirus infection, interstitial lung disease, degenerative disease of the nervous system, congenital rubella infection, cancer in brain or meninges.
      <.00001
      Significant p-value.
       Yes23 (4.7)12 (0.3)
       No462 (95.3)4,346 (99.7)
      Parental civil status,
      Information on parental civil status was missing for 42 children, 28 children for parental income, and 3 for parental work status.
      n (%)
      .598
       Single52 (10.7)519 (11.9)
       Not single419 (86.4)3,811 (87.4)
      Parental income
      Information on parental civil status was missing for 42 children, 28 children for parental income, and 3 for parental work status.
      ,
      One Danish Krøne equals 0.13 Euro.
      (DKK), mean (SD)
      221,230 (101,047)233,355 (160947).021
      Significant p-value.
       Parental work status,
      Information on parental civil status was missing for 42 children, 28 children for parental income, and 3 for parental work status.
      n (%)
      <.00001
      Significant p-value.
       Outside workforce58 (12.0)253 (5.8)
       One or both parent(s) at work425 (87.6)4,104 (94.2)
      Parental mental disorders.192
       None398 (82.1)3,467 (79.6)
       One or both parent(s)87 (17.9)891 (20.4)
      DKK = Danish Krøne; SD = standard deviation.
      a P value: Likelihood ratio test in a conditional logistic regression.
      b Significant p-value.
      c Severe somatic diseases: congenital syndrome: microcephaly, megalencephaly, Smith–Lemi–Opitz' syndrome, trisomy 21, Down's syndrome, partial autosomal trisomy, cytomegalovirus infection, interstitial lung disease, degenerative disease of the nervous system, congenital rubella infection, cancer in brain or meninges.
      d Information on parental civil status was missing for 42 children, 28 children for parental income, and 3 for parental work status.
      e One Danish Krøne equals 0.13 Euro.
      The incidence of any mental disorder (21.8%), neurodevelopmental disorder (15.4%), and other mental disorder (9.0%) was significantly higher in children with cataract who had somatic comorbidities compared with children with isolated cataract (any mental disorders, 8.4%; neurodevelopmental disorders, 5.8%; and other mental disorders, 2.3%) (Table 2).
      TABLE 2Background Characteristics of Children with Cataract (n = 485).
      Isolated CataractCataract and Severe Somatic DiseasesP value
      P value: Pearson's χ2 test for categorical variables, t test for continuous variables.
      (n = 407)(n = 78)
      Sex, girls/boys, n (%)197/210 (48.4/51.6)45/33 (57.7/42.3).168
      Age at cataract diagnosis (years), median (IQR)1.4 (0.19–5.1)0.6 (0.14–4.4).344
      Age at surgery time (years), median (IQR)2.1 (0.3–4.9)0.6 (0.2–4.0).243
      Number of operated/number of nonoperated (%)232/175 (57.0/43.0)50/28 (64.1/35.9).299
      Unilateral/bilateral surgery (%)131/101 (32.2/24.8)12/38 (24.0/76.0).003
      Significant p-value.
      Children with any mental disorders
      Each child could be diagnosed with different mental disorders. The number of children with neurodevelopmental and other mental disorders, therefore, does not add up to the number of children with any mental disorders.
      (%)
      34 (8.4)17 (21.8).0008
      Significant p-value.
      Children with neurodevelopmental disorder (%)28 (5.8)12 (15.4).023
      Significant p-value.
      Children with emotional/affective disorders (%)11 (2.3)7 (9.0).018
      Significant p-value.
      IQR = interquartile range.
      a P value: Pearson's χ2 test for categorical variables, t test for continuous variables.
      b Significant p-value.
      c Each child could be diagnosed with different mental disorders. The number of children with neurodevelopmental and other mental disorders, therefore, does not add up to the number of children with any mental disorders.
      Children with cataract were twice as likely to have a mental disorder as children without cataract: 10.5% (n = 51/485) and 5.2% (n = 225/4358), respectively (OR, 1.83; 95% CI, 1.28–2.63; P = .0009) in analyses adjusted for geographical birth origin, somatic disease confounders, socioeconomic status, and parental mental disorders. A particularly high incidence of mental disorders was seen in children diagnosed with cataract during their first 3 years of life (n = 35/327 [10.7%]), compared with age-matched children without cataract (n = 118/2912 [4.1%]; OR, 2.36; 95% CI, 1.53–3.64; P = .0001), whereas we did not find a significantly increased risk in children diagnosed with cataract after 3 years of age compared with an age-matched cohort (Table 3). When we subgrouped the children with cataract and without cataract into those with and without severe somatic disease (isolated cataract), the risk of any mental disorder (adjusted OR, 1.72; 95% CI, 1.15-2.58; P = .009) and neurodevelopmental mental disorder (adjusted OR, 2.07; 95% CI, 1.31–3.26; P = .002) remained higher in those with isolated cataracts (Supplementary Table 4).
      TABLE 3Incidence of Mental Disorders among Children with and without Cataract.
      Children with CataractChildren without CataractUnadjustedAdjusted
      Adjusted for parental socioeconomic status, family psychiatric load and the children's severe somatic comorbidity (congenital syndrome: microcephalia, megalencephaly, Smith–Lemi–Opitz syndrome, trisomy 21, downs syndrome, partial autosomal trisomy, cytomegalovirus infection, interstitial lung disease, degenerative disease of the nervous system, congenital rubella infection, cancer in brain or meninges)
      (n = 485)(n = 4358)OR (95% CI)P valueOR (95% CI)P value
      Any mental disorders51/485 (10.5)225/4358 (5.2)2.16 (1.57–2.78)<.00001b1.83 (1.28–2.63).0009
      Significant p-value.
      b
       0–3 years
      Age at cataract onset.
      35/327 (10.7)118/2912 (4.1)2.84 (1.91–4.22)<.00001b2.36 (1.53–3.64).0001
      Significant p-value.
       4–10 years
      Age at cataract onset.
      16/158 (10.1)107/1446 (7.4)1.41 (0.81–2.45).2241.24 (0.66–2.30).504
      Neurodevelopmental disorders40/485 (8.2)148/4358 (3.4)2.56 (1.78–3.67)<.00001b2.05 (1.35–3.11).0007
      Significant p-value.
       0–3 years
      Age at cataract onset.
      28/327 (8.6)77/2912 (2.6)3.45 (2.20–5.40)<.00001b2.64 (1.59–4.4).0002
      Significant p-value.
       4–10 years
      Age at cataract onset.
      12/158 (7.6)71/1446 (4.9)1.59 (0.84–3.00).1521.37 (0.68–2.76).376
      Other mental disorders18/485 (3.7)95/4358 (2.2)1.73 (1.04–2.89).036b1.69 (1.0–2.87).052
       0–3 years
      Age at cataract onset.
      12/327 (3.7)50/2912 (1.7)2.18 (1.15–4.14).017b2.22 (1.18–4.18).014
      Significant p-value.
       4–10 years
      Age at cataract onset.
      6/158 (3.8)45/1446 (3.1)1.23 (0.52–2.98).6421.12 (0.40–2.85).814
      OR = odds ratio.
      Values are n/N (%).
      a Adjusted for parental socioeconomic status, family psychiatric load and the children's severe somatic comorbidity (congenital syndrome: microcephalia, megalencephaly, Smith–Lemi–Opitz syndrome, trisomy 21, downs syndrome, partial autosomal trisomy, cytomegalovirus infection, interstitial lung disease, degenerative disease of the nervous system, congenital rubella infection, cancer in brain or meninges)
      b Significant p-value.
      c Age at cataract onset.
      When we subgrouped the cataract children with and without cataract surgery, the risk of any mental disorder (adjusted OR, 2.26; 95% CI, 1.46–3.50; P = .0002), neurodevelopmental mental disorders (adjusted OR, 2.42; 95% CI, 1.46–3.99; P = .0006) and other mental disorders (adjusted OR, 2.34; 95% CI, 1.23–4.43; P = .0092), was significant higher among cataract children with surgery (Supplementary Table 5).
      The risk of neurodevelopmental disorders was doubled in the cataract group (OR, 2.05; 95% CI, 1.35–3.11; P = .0007) after adjustment for confounders (Table 3). The most frequent neurodevelopmental disorder was developmental delay (n = 22/485 [4.5%]) followed by ASD (n = 11/485 [2.3%]), and ADHD (n = 6/485 [1.2%]). The risk of developmental delay was higher in the cataract group than in the control group (OR, 2.66; 95% CI, 1.45–4.90; P = .0017), whereas we did not find a significantly increased risk of ASD (OR, 1.62; 95% CI, 0.78–3.39; P = .192) or attention deficit/hyperactivity disorders (OR, 1.31; 95% CI, 0.50–3.46; P = .581) in the children with cataract compared with children without cataract.
      Children with cataract also had an overall higher risk of having a mental disorder of not primary neurodevelopmental origin in crude analyses (OR, 1.73; 95% CI, 1.04–2.89; P = .036), but became insignificant in analyses adjusting for several confounders (OR, 1.69; 95% CI, 1.0–2.87; P = .052). The risk of anxiety disorders was quadrupled in children with cataract (n = 10/485 [2.1%]; OR, 4.10; 95% CI, 1.90–8.84; P = .0003). In addition, an increased tendency of eating disorders was observed (OR, 4.19; 95% CI, 0.72–24.44; P = .111).

      DISCUSSION

      This study is the first to explore a broad range of mental disorders in children with cataract comparing the incidence in these children with the age- and sex-matched background population based on diagnoses made by medical doctors. We used nationwide population registries to account for the potential influences of a range of confounders, including somatic comorbidities, the socioeconomic status of the family, and parental mental disorders. The risk of anxiety disorders was increased more than 4-fold, and the risk of neurodevelopmental delay was increased 2-fold in children with cataract. The risk was highest among children diagnosed with cataract before 3 years of age. In addition, the risk of mental disorders was highest in the group of children who had cataract in combination with systemic disease. Furthermore, mental disorders were increased for those cataract children who have undergone cataract surgery. However, it is difficult to distinguish whether the increased mental disorders is caused by the surgery itself, the visual impairment, or the pathology of the cataract.
      Whereas the increased risk of neurodevelopmental disorders in children with cataract was expected, the 4-fold risk of anxiety disorders was a remarkable finding but in line with finding from studies of other chronic diseases in childhood, such as epilepsy
      • LaGrant B
      • Marquis BO
      • Berg AT
      • Grinspan ZM.
      Depression and anxiety in children with epilepsy and other chronic health conditions: national estimates of prevalence and risk factors.
      and diabetes type I.
      • Dybdal D
      • Tolstrup JS
      • Sildorf SM
      • et al.
      Increasing risk of psychiatric morbidity after childhood onset type 1 diabetes: a population-based cohort study.
      Children with cataract are exposed to repeated examinations under anesthesia and hospital appointments and at-home patching therapy for amblyopia,
      • Yorston D.
      Surgery for congenital cataract.
      ,
      • Austerman J.
      ADHD and behavioral disorders: assessment, management, and an update from DSM-5.
      and they may suffer from visual impairment associated with cataract, which influence social interactions, for example, response to facial expressions.
      • Foster A
      • Gilbert C
      • Rahi J.
      Epidemiology of cataract in childhood: a global perspective.
      ,
      • DeCarlo DK
      • Swanson M
      • McGwin G
      • Visscher K
      • Owsley C.
      ADHD and vision problems in the National Survey of Children's Health.
      ,
      • Wrzesińska M
      • Kapias J
      • Nowakowska-Domagała K
      • Kocur J.
      Visual impairment and traits of autism in children.
      It is already well-known that blind and visually impaired young people face an increased risk of depression and anxiety.
      • Lopes N
      • Dias LLDS
      • Ávila M
      • et al.
      Humanistic and economic burden of blindness associated with retinal disorders in a Brazilian sample: a cross-sectional study.
      • Augestad LB.
      Mental health among children and young adults with visual impairments: a systematic review.
      • Ishtiaq R
      • Chaudhary MH
      • Rana MA
      • Jamil AR.
      Psychosocial implications of blindness and low vision in students of a school for children with blindness.
      Importantly, our incidence of anxiety disorders may be underestimated as anxiety often presents during adolescence
      • Dalsgaard S
      • Thorsteinsson E
      • Trabjerg BB
      • et al.
      Incidence Rates and cumulative incidences of the full spectrum of diagnosed mental disorders in childhood and adolescence.
      and we only included children up to the age of 10 years.
      For comparison, only a limited number of studies have been published in which mental health problems and disorders have been investigated in children with cataract. In a Chinese study of 119 children who were between 3 and 8 years of age, children with cataract used the Conners Parent Rating Scale and found a doubling in the incidence of conduct problems, learning problems, psychosomatic, impulsiveness/hyperactivity, and anxiety problems compared with 143 children without cataract.
      • Lin Z-L
      • Lin D-R
      • Chen J-J
      • et al.
      Increased prevalence of parent ratings of ADHD symptoms among children with bilateral congenital cataracts.
      This study is consistent with our findings based on diagnoses made by medical doctors using the ICD-10 criteria. In a previously study of Danish children with cataract, we found that the subjective visual function related to academic achievements was rated as poor,
      • Hansen MM
      • Bach-Holm D
      • Kessel L.
      Visual outcomes after surgery for childhood cataracts.
      which is in line with the parental assessment of learning problems in the Chinese study. In contrast with the Chinese study, we did not find a statistically significant higher incidence of impulsiveness/hyperactivity–related diagnoses. Our study was based on mental disorders diagnosed in a hospital setting where only the most seriously affected children exceed the threshold for referral. A study of 41 British children aged 5 to 19 years with congenital cataracts found a lower psychosocial health level in these children compared with children with other systemic diseases,
      • Chak M
      • Rahi JS.
      The health-related quality of life of children with congenital cataract: findings of the British Congenital Cataract Study.
      which supports our findings.
      Severe somatic disease may be directly linked to both development of cataract and presence of mental disease.
      • Harbord MG
      • Baraitser M
      • Wilson J.
      Microcephaly, mental retardation, cataracts, and hypogonadism in sibs: Martsolf's syndrome.
      • Hered RW.
      Pediatric ophthalmology and strabismus, Section 6.
      • Chess S
      • Fernandez P
      • Korn S.
      Behavioral consequences of congenital rubella.
      • Chauhan N
      • Sen MS
      • Jhanda S
      • Grover S.
      Psychiatric manifestations of congenital rubella syndrome: a case report and review of literature.
      • Gentile I
      • Zappulo E
      • Riccio MP
      • et al.
      Prevalence of congenital cytomegalovirus infection assessed through viral genome detection in dried blood spots in children with autism spectrum disorders.
      • Shaw D
      • Bar S
      • Champion JD.
      The impact of developmental behavioral pediatrics in a population of children with Down syndrome.
      • da Cunha RP
      • Moreira JB.
      Ocular findings in Down's syndrome.
      We found a doubling of the risk of unspecific developmental delay disorder in children with cataract also in analyses adjusting for diseases with known neurodevelopmental comorbidity and diseases in which the treatment involves potential adverse neurodevelopmental exposures.
      • Jobling AI
      • Augusteyn RC.
      What causes steroid cataracts? A review of steroid-induced posterior subcapsular cataracts.
      ,
      • MacKenzie EM
      • Odontiadis J
      • Le Mellédo J-M
      • Prior TI
      • Baker GBI
      The relevance of neuroactive steroids in schizophrenia, depression, and anxiety disorders.
      ,
      • Chodick G
      • Sigurdson AJ
      • Kleinerman RA
      • et al.
      The risk of cataract among survivors of childhood and adolescent cancer: a report from the Childhood Cancer Survivor Study.
      • Willard VW
      • Berlin KS
      • Conklin HM
      • Merchant TE.
      Trajectories of psychosocial and cognitive functioning in pediatric patients with brain tumors treated with radiation therapy.
      • Willard VW
      • Conklin HM
      • Wu S
      • Merchant TE.
      Prospective longitudinal evaluation of emotional and behavioral functioning in pediatric patients with low-grade glioma treated with conformal radiation therapy.
      Our findings highlight the psychological burden on children living with chronic somatic disease. In some situations, the psychological load may influence treatment outcome, as shown in studies of children and adolescents with type I diabetes mellitus.
      • Sildorf SM
      • Breinegaard N
      • Lindkvist EB
      • et al.
      Poor metabolic control in children and adolescents with type 1 diabetes and psychiatric comorbidity.
      ,
      • Jin J
      • Sklar GE
      • Min Sen Oh V
      • Chuen Li S.
      Factors affecting therapeutic compliance: a review from the patient's perspective.
      ,
      • Roohafza H
      • Kabir A
      • Sadeghi M
      • et al.
      Stress as a risk factor for noncompliance with treatment regimens in patients with diabetes and hypertension.
      The management of childhood cataract often includes patching of the better seeing eye to improve vision in the poorer seeing eye (amblyopia treatment).
      • Lambert SR
      Childhood cataracts.
      Compliance is essential for visual outcome in amblyopia treatment. The treatment of amblyopia can be associated with a high degree of distress, increased stigma, and logistical problems for children and parents.
      • Loudon SE
      • Passchier J
      • Chaker L
      • et al.
      Psychological causes of non-compliance with electronically monitored occlusion therapy for amblyopia.
      • Hrisos S
      • Clarke MP
      • Wright CM.
      The emotional impact of amblyopia treatment in preschool children: randomized controlled trial.
      • Dixon-Woods M
      • Awan M
      • Gottlob I.
      Why is compliance with occlusion therapy for amblyopia so hard? A qualitative study.
      We were not able to discern whether amblyopia therapy contributed to the increased risk of anxiety in our cataract population, but attention should be paid to the mental vulnerability of the child and treatment adjusted based on a holistic perspective.

       STRENGTHS AND LIMITATIONS

      The major strength of this population-based registry study is its nationwide character with no attrition bias. Mental disorders were diagnosed by medical doctors in hospital settings in accordance with ICD-10 diagnostic criteria. To ensure that the interaction of other confounders was minimized, we adjusted for relevant variables such as geographical birth origin, disease confounders, parental socioeconomic status, and parental mental disorders. Conversely, this study also has some limitations. There may be a risk of selection bias because children seen and treated by child psychiatrists working in private practice are not always reported into the NPR, which may result in an underestimated true incidence of mental disorders. In addition, referral bias must be considered, because children with cataract are treated in hospital settings and therefore have a higher odds of being referred and diagnosed with a mental disorder. However, some families may also decline referral because they already have to deal with cataract, or they may interpret the child's behavior as related to the eye disease.
      In this nationally representative sample, we found a markedly higher incidence of developmental disorders and anxiety among children with cataract compared with the background pediatric population. The associations between childhood cataract and mental disorders remained significant even after adjusting for relevant factors such as disease confounders and parental socioeconomic status and psychiatric disease. An increased awareness of the mental health burden associated with childhood cataract is important. Routine screening of mental health, for example, using the Strengths and Difficulties Questionnaire,
      • Goodman R.
      The Strengths and Difficulties Questionnaire: a research note.
      could guide the support to these children taking into account their mental health as well as overall quality of life, in the visual and optical rehabilitation.
      All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
      Funding/Support: The study received financial support from Øjenforeningen (Fight for Sight Denmark) and Carl and Nicoline Larsen´s Fund, Synoptik Foundation and Øjenfonden. The funding bodies had no influence on conception, design or reporting of the study. None of the authors have any conflicts of interests to declare.

      Appendix. Supplementary materials

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