Temporal changes in incidence, prevalence and causes of childhood visual impairment - Learnings from 45 years with the National Danish Registry of Children with Visual Impairment.

PURPOSE: The aim of the study was to describe the temporal changes in causes and prevalence of childhood visual impairment in Denmark based on the National Danish Registry of Children with Visual Impairment (NDRCVI). METHODS: Annual reports on the NDRCVI since its establishment in 1979 were reviewed and data on the number of registered children and the causes for registration with a visual impairment were evaluated. RESULTS: The average annual incidence of childhood visual impairment in Denmark is 2.8 per 1000 live-born children and the prevalence of childhood visual impairment is 1.6 per 1000 children <18 years. Today, fewer children are severely visually impaired (visual acuity ≤6/60) at the time of registration (31.6% since 2010 vs. 51.1% in the 1980s). Cerebral visual impairment and optic nerve atrophy have remained common causes of childhood visual impairment whereas sequelae to retinopathy of prematurity have been almost eliminated as a cause. Systemic comorbidities are more common now in children with visual impairment (seen in 63.9% in the last decades vs. 44.6%in the 1980-ties). CONCLUSION: Whereas the prevalence of visual impairment has remained relatively stable over the years, the severity of visual impairment has improved, suggesting that more children will be able to live an active life supported by aids compensating vision loss. However, more children have systemic comorbidities in combination with their visual impairment suggesting that children with visual impairment face a life not only limited by the obstacles of poor vision. This calls for multidisciplinary management and support of affected children and families.

Blindness is decreasing among children born preterm during the last four decades in Denmark.

PURPOSE: Children born preterm are believed to be at increased risk of visual impairment (VI). The increased survival rate of extremely preterm children may have changed the spectrum of diseases occurring postnatally. The aim of this study was to analyse the prevalence and causes of VI in an ex-preterm Danish population during the last 4 decades. METHODS: The study was based on the National Register of Blind and Visually Impaired Children (NRVIC). Ex-preterms born at gestational age (GA) <32 weeks and enrolled in NRVIC at any time between 1988 and 2020 were included. The main cause of VI, the severity of VI and systemic comorbidities were analysed for temporal changes. RESULTS: A total of 335 patients were included. The prevalence of VI decreased from 26/1000 preterm children in the 1980s to 15/1000 in 2000s. Blindness due to preterm birth is almost eliminated affecting 1/1000 today. Sequelae to retinopathy of prematurity (ROP) was the most common cause of VI (51% of cases) in the 1980s but decreased to 34% in 2010s, whereas non-ocular causes of VI increased from 1% to 36%, respectively. More than half of the children (64%) had combined comorbidities and 36% had isolated VI. CONCLUSION: The improved monitoring in neonatal intensive care units and management of ROP has reduced the prevalence of severe VI due to ROP and almost eliminated blindness over the last decades in Denmark. However, preterm children are still at risk of non-ocular causes of VI and comorbidities following the premature delivery.

Nystagmus in children with primary brain tumours in Denmark between 2007 and 2017.

BACKGROUND: The aim of the study was to evaluate the prevalence, clinical characteristics, and diagnostic importance of nystagmus in children with brain tumours. METHODS: A nation-wide retrospective review of all children diagnosed with a brain tumour between January the 1st, 2007 and December 31st, 2017, in Denmark. Data is based on information from the Danish Childhood Cancer Registry, hospital records from paediatric- and ophthalmological departments, and records from private ophthalmologists. RESULTS: Nystagmus was observed in 13.7% (60/437) of children with a brain tumour. In 50/60 children (83.3%) nystagmus was an incidental finding at the clinical examination and only in 10/60 children (16,7%) were nystagmus noticed by patient/caregivers prior to the clinical examination. In 38/60 children nystagmus was observed before the brain tumour diagnosis, most often (16/38, 42%) the same day as the diagnosis was made. In 22/60 children nystagmus was found after the brain tumour diagnosis (prior to any treatment) with a median of four days (range 0-47) after the brain tumour diagnosis. Nystagmus was most commonly binocular (56/60, 93.3%) and gaze-evoked (43/60, 71.7%). The median number of additional symptoms and/or clinical findings was five (range 0-11). CONCLUSION: Nystagmus is frequent in children with brain tumours and is typically accompanied by other symptoms and clinical signs. However, nystagmus is often first recognized by the ophthalmologist late in the time course. Therefore, raising awareness of the importance of looking for nystagmus in children with unspecific neurological symptoms might contribute to increased suspicion of brain tumour and thereby faster diagnosis.

Ophthalmic symptoms, clinical signs and diagnostic delay in infants diagnosed with brain tumours in Denmark between 2007 and 2017.

PURPOSE: To investigate ophthalmic onset manifestations and the impact of diagnostic delay on the prognosis in infants (<1 year) diagnosed with a brain tumour. METHODS: A retrospective population-based nationwide study of infants diagnosed with a brain tumour between 2007 and 2017 in Denmark. Data was retrieved from the Danish Childhood Cancer Registry, the National Danish Health registries, and medical files. Primary outcome measures included symptoms, clinical findings, time to diagnosis and survival. RESULTS: Thirty-seven infants were diagnosed with a brain tumour in Denmark between 2007 and 2017. In total, 19/37 infants (51%, 95% CI: 34-68) had ophthalmic manifestations at any time prior to or at diagnosis; and in 6/37 (16%, 95% CI: 6-32) ophthalmic manifestations were the initial symptom. The most common ophthalmic manifestations were strabismus (n = 7), sunset eyes (n = 6), nystagmus (n = 4), reduced pupillary light reflex (n = 4), and/or decreased vision (n = 4). The median number of symptoms per infant at the time of diagnosis was three (range 0-9). The median diagnostic delay was 26 days (range 0-283, IQR: 6;90). 5-year survival rate was 75% (95% CI: 61-90) and all children with diagnostic delay > 100 days (n = 9, 24%) were still alive at the end of follow-up (median 6.3 years, range 2.2-10.2). CONCLUSION: We provide an overview of symptoms and clinical signs in a nation-wide series of infants with CNS tumours and demonstrate that ophthalmic manifestations are frequently observed in infants prior to diagnosis, but, often in combination with other clinical signs. The diagnostic delay was substantial for a large part of the infants, but this was not associated with increased mortality.

Support needs around the time of diagnosis of parents caring for an infant with visual impairment or blindness in Denmark: a qualitative study.

OBJECTIVE: The whole family is affected when an infant is diagnosed with visual impairment or blindness. We aimed to describe the support needs of parents around the time of diagnosis. DESIGN: We used a descriptive qualitative method based on the theory of critical psychology and conducted five semistructured interviews with a total of eight parents of children under the age of 2 years who had been diagnosed with blindness or visual impairment before the age of 1 year. Thematic analysis was used to extract primary themes. SETTING: The study was initiated by a tertiary hospital centre specialised in the ophthalmic management of children and adults with visual impairment. PARTICIPANTS: Eight parents representing five families caring for a child under the age of 2 years with visual impairment or blindness participated in the study. The parents were recruited from the Department of Ophthalmology at Rigshospitalet, Denmark in relation to appointments in the clinic or by phone or email. RESULTS: We identified three themes: (1) recognition and reactions during the time of diagnosis; (2) family, network and struggles; and (3) interaction with healthcare professionals. CONCLUSION: The main lesson for healthcare professionals is to bring hope at a time when all hope may seem to be lost. Second, a need to direct attention to families with no or sparse supportive networks. Third, coordinating appointments between hospital departments and at-home therapies and reducing the number of appointments to allow parents time to establish a family relation with their child. Parents respond well to competent healthcare professionals who keep them informed and who see their child as an individual rather than as a diagnosis.

Longitudinal analysis of health care costs in patients with childhood onset inherited retinal dystrophies compared to healthy controls.

BACKGROUND: We evaluated health care costs in patients with childhood onset visual impairment caused by inherited retinal dystrophies (IRD). METHODS: The IRD cohort, identified from the Danish Registry of Blind and Partially Sighted Children, was compared to age- and sex-matched controls from the national, Danish population registry. Information on health care expenditures for somatic and psychiatric in- and outpatient services, purchase of prescription medications and paid assistance at home were obtained from national registries for the years 2002-2017. RESULTS: We included 412 in the IRD cohort (6,290 person years) and 1656 (25,088 person years) in the control cohort. Average, annual health care expenditures from age 0-48 years of age were €1,488 (SD 4,711) in the IRD cohort and €1,030 (4,639) in the control cohort. The largest difference was for out-patient eye care (13.26 times greater, 95% confidence interval 12.90-13.64). Psychiatric in-patient expenditures were 1.71 times greater (95% CI 1.66-1.76) in the IRD cohort but psychiatric out-patient health care costs were comparable between groups. CONCLUSIONS: Health care costs were approximately 40% greater in the IRD cohort compared to an age- and sex-matched sample from the general Danish population. This is relevant in the current situation with a number of trials aimed at treating IRDs using genetically based therapies. Although eye care expenditures were many times greater, they made up < 10% of the total health care expenditures even in the IRD cohort. The reduced costs related to injuries in the visually impaired cohort was a surprising finding but may reflect a reduced propensity to seek medical care rather than a reduced risk of injuries.

Childhood-onset retinal dystrophies reduces life-time income by one third - an individual based socio-economic analysis.

BACKGROUND: The aim of this study was to evaluate lifetime income, educational level and workforce participation in patients with childhood-onset inherited retinal dystrophies (IRD). MATERIAL AND METHODS: The registry-based study using national, Danish databases on education, income, employment and social benefits in a cohort of 515 patients with childhood-onset IRD and without severe systemic comorbidities matched 1:4 to an age- and sex to a control sample of the Danish background population. Socio-economic status was modelled with focus on grade mark points after primary education, highest attained education at 30 years or age, employment and unemployment rate, disability pension and lifetime income. RESULTS: At 30 years of age, the proportion of those who had primary education as the highest achieved level was higher in the IRD group (35.4% versus 18.7%) and they were more likely to be receiving a disability pension (OR 11.77) or be unemployed (OR 6.63). Those at work had the same number of work hours as the control group, and the same proportion had obtained a Master or PhD degree (14%). At 30 years of age, income earnings were lower in the IRD group and the lifetime income was reduced by 30%. CONCLUSION: A few among those with childhood-onset IRD were able to obtain high educational levels, and many were assigned a disability pension from early adulthood or were unemployed, resulting in a markedly reduced lifetime income although grade mark points from primary education were comparable, suggesting that the difference was not explained by intellectual differences between the groups.

Medical and surgical treatment of rhino-orbital-cerebral mucormycosis in a child with leukemia.

PURPOSE: Rhino-orbital-cerebral mucormycosis (ROCM) is a rare opportunistic infection with a high mortality despite relevant treatment. OBSERVATIONS: A 3-year-old girl under treatment for acute lymphoblastic leukemia developed periorbital swelling, ophthalmoplegia and a necrotic palatal lesion during a period of neutropenia. Imaging revealed sinusitis, pre- and postseptal cellulitis. The disease later progressed to cerebral involvement and orbital apex syndrome with complete ophthalmoplegia, ptosis and loss of vision. The patient was treated with systemic antifungal therapy, hyperbaric oxygen and extensive surgery. This included orbital exenteration, skull base resection, cerebral debridement with placement of an Ommaya reservoir for intrathecal administrations of amphotericin B (AmB) and in addition endoscopic sinus surgery with local AmB installation. Chemotherapy was safely continued after resolution of the ROCM and the patient remains in complete remission after 5 years. CONCLUSION AND IMPORTANCE: Patients with ROCM can be cured with aggressive multimodality treatment, including surgical intervention, even if in myelosuppression.

Prevalence and causes of infantile nystagmus in a large population-based Danish cohort.

PURPOSE: The aim of this study was to provide a population-based estimate on the prevalence of infantile nystagmus and to describe the causes in the Capital Region of Denmark. METHODS: Review of medical records of children with infantile nystagmus born in the period 1 January 2010 through 31 December 2017 and living in the Capital Region of Denmark. We used birth registry data from Statistics Denmark and the National Danish Birth Registry to calculate the prevalence of nystagmus in children born at term and prematurely. RESULTS: A total of 103 patients (52 males/51 females) with infantile nystagmus were included. The overall prevalence of infantile nystagmus was 6.1 per 10 000 live births. It was higher in premature children (28.4/10 000 live births) than children born at term (4.4/10 000), p < 0.0001, and highest in children born extremely preterm, (97.3/10 000). The most common cause of infantile nystagmus was ocular disease (44%) followed by idiopathic nystagmus (32%), neurological disorders and genetic syndromes (20%) and prematurity without retinopathy of prematurity as the only cause (4%). CONCLUSIONS: In this study, we provide the prevalence of infantile nystagmus based on national medical records in which all residents are accounted for. Our findings show a prevalence of 6.1 per 10 000 live births but six times higher among children born preterm than born at term. Ocular disease was the leading cause of infantile nystagmus with albinism and ocular malformations as the most frequent. In 1/3 of patients, no cause could be identified.

As-indicated versus routine vision screening of preterm children: a 17-year retrospective regional study.

PURPOSE: To investigate outcomes of routine vision screening compared to as-indicated ophthalmological investigation of all children born preterm in a Danish region from 1997 to 2014. METHODS: All children born preterm (gestation age < 32 weeks or birthweight < 1500 g) screened for retinopathy of prematurity (ROP) were divided into two groups. From 1997 to 2009, only children treated for ROP or referred for visual problems received ophthalmological investigation (as-indicated group). From 2010 to 2014, all ROP-screened infants were offered ophthalmological investigation at 6 months and 3 years of age (screening group). RESULTS: A total of 560 children were included in the as-indicated period, 41 and 87 were referred for ophthalmological investigation at 6 months and 3 years, respectively. In the screening period, 295 children were included, 251 and 150 of whom underwent vision evaluation at 6 months and 3 years, respectively. Mean visual acuity was 4.1 cycles per degree with Teller acuity cards at 6 months and 0.78 decimal at 3 years. At 3 years, 2.7%(n = 11) in the as-indicated versus 3.5%(n = 10) screening group had visual acuity < 6/18 (p = 0.24). Cerebral palsy (n = 28) and epilepsy (n = 5) were significantly related to vision impairment (p = 0.001/0.006), while treated ROP was not (n = 13). Refractive error was common at 3 years (61%), especially astigmatism (50%). Gestational age, birthweight and ROP were not associated with vision impairment or refractive error. CONCLUSION: Screening preterm children at 6 months and 3 years did not reveal more visually impaired children compared to examination when indicated.

A study of familial Char syndrome involving the TFAP2B gene with a focus on facial shape characteristics.

In this case study, we investigate a child presenting with patent ductus arteriosus, short philtrum, duck-bill lips, strabismus, a flat nasal bridge, a broad forehead, low-set ears, hypertelorism, up-slanting palpebral fissures, almond-shaped eyes, and hypodontia, all leading to the clinical diagnosis of Char syndrome. Genetic analysis showed heterozygosity for the novel variant c.851T>C, p. Leu284Ser in the TFAP2B gene. Family analysis suggested that at least 20 members, extending six generations back, were affected. All 10 members available for genetic testing were heterozygous for the novel pathogenic variant. Qualitative analysis of the facial dysmorphology in the proband and three of the affected family members using three-dimensional surface scanning showed that the major deviations were observed in the forehead/eyebrow, nose, upper lip, and chin regions with, for example, a flattened nose and reduced height of the upper lip and the face. Furthermore, it is suggested that Char syndrome is associated with disturbances of tooth formation and eruption.

Predictors of visual outcome in patients operated for craniopharyngioma - a Danish national study.

PURPOSE: Craniopharyngioma often causes visual loss due to the close relation to the anterior visual pathways. This study investigates the incidence and predictors of visual outcomes in patients with craniopharyngioma. METHODS: Data from sixty-six patients who underwent surgery for craniopharyngioma from 2009 to 2013 in Denmark were reviewed. Primary outcomes were visual acuity (VA) and visual field (VF) defects from pre-and postoperative visits. Secondary outcomes were optic nerve atrophy (OA) and papilledema. RESULTS: Fifty-eight patients were included. The VA of the patients 1-year after surgery improved by -0.16 log(MAR) (95%CI: -0.30 to -0.02; p = 0.0266). Visual field (VF) defects worsened in 17 eyes (30%), remained stable in 21 eyes (37%) and improved in 19 eyes (33%). The presence of papilledema and the absence of OA were significantly correlated with an improvement in VA postoperatively (p = 0.011 and p = 0.011, respectively). Patients undergoing surgery within a week or less after their first ophthalmological examination had a significant improvement in VA (-0.36; 95%CI: -0.62 to -0.09; p = 0.0099). Patients undergoing surgery using a subfrontal approach also showed improvement in VA (p = 0.048). Tumour recurrence had a significantly worse VA outcome (p = 0.0074). CONCLUSION: Patients show a slight improvement in VA 1-year after operation for craniopharyngioma. The presence of papilledema and early surgical intervention is associated with a significant improvement in VA. Early involvement of a dedicated ophthalmologist is recommended to secure an early detection of a visual decline and potential tumour recurrence.

Crouzon syndrome associated with acanthosis nigricans: prenatal 2D and 3D ultrasound findings and postnatal 3D CT findings.

Crouzon syndrome with acanthosis nigricans (CAN) is a very rare condition with an approximate prevalence of 1 per 1 million newborns. We add the first report on prenatal 2D and 3D ultrasound findings in CAN. In addition we present the postnatal 3D CT findings. The diagnosis was confirmed by molecular testing.

A new risk-based screening criterion for treatment-demanding retinopathy of prematurity in Denmark.

OBJECTIVE: The aim of this study was to uncover the most effective and safe criterion to implement for retinopathy of prematurity screening in Denmark. METHODS: This retrospective national cohort study is based on data from 3 national registers. These registers provided on infants treated for retinopathy of prematurity, infants in need of treatment but missed by the present screening program, and the candidate neonates for advanced retinopathy of prematurity development A nonlinear logistic regression model was fitted to the data, and various screening criteria were evaluated. RESULTS: During the study period (2002-2006), 116 infants were treated for retinopathy of prematurity, no treatment-demanding retinopathy of prematurity infants were missed by the screening program, and 182 premature infants were candidates for developing treatment-demanding retinopathy of prematurity. Screening criteria combining gestational age at delivery and birth weight limits and new risk-based criteria were compared with regards to their effectiveness. The risk-based criteria were the most effective. Use of the 0.13% risk-based criterion to define the population to be screened resulted in the detection of all treated infants in the study period and 17.4% fewer infants to screen. The model predicted this criterion to result in 1 missed case of treatment-demanding retinopathy of prematurity every 11 years and 1 case of blindness every 18 years in Denmark. CONCLUSIONS: Screening criteria based on risk estimates of developing treatment-demanding retinopathy of prematurity are the most effective for retinopathy-of-prematurity screening. The risk-based criterion of 0.13% can safely be implemented for future retinopathy-of-prematurity screening in Denmark.

Treatment for retinopathy of prematurity in Denmark in a ten-year period (1996 2005): is the incidence increasing?

OBJECTIVE: The objective of this study was to analyze the population incidence of retinopathy of prematurity treatment in Denmark in the 10-year period from 1996 to 2005. METHODS: Patient charts of infants treated for retinopathy of prematurity and the national birth registry provide information about neonatal parameters. These parameters, along with birth in the latter half of the period (2001-2005), were analyzed as risk factors for retinopathy of prematurity. The national registry for blind and visually impaired children was accessed to obtain information about visual impairment attributable to retinopathy of prematurity in both treated and untreated infants. RESULTS: The study population consisted of 5467 Danish preterm infants born in 1996 to 2005, with a gestational age of < 32 weeks, who survived for > or = 5 postnatal weeks; 2616 were born in 1996 to 2000, and 2851 were born in 2001 to 2005. The incidence of treated retinopathy of prematurity cases increased significantly from 1.3% in 1996 to 2000 to 3.5% in 2001 to 2005. Significant risk factors for retinopathy of prematurity treatment were low gestational age, small for gestational age, male gender, and multiple birth. Other, yet unknown factors contributed to the increased incidence in the latter half of the period. Of the study population, 0.6% were registered as visually impaired because of retinopathy of prematurity within 2 years after birth (early-detected visual impairment). The incidences were not significantly different between 1996 to 2000 and 2001 to 2005. Of all of the early-detected, visually impaired children, 16% had not been treated for retinopathy of prematurity and were considered screening failures. CONCLUSIONS: The incidence of retinopathy of prematurity treatment in Denmark has more than doubled during the past half-decade. This increase could not be fully explained by increased survival rates for the infants or by changes in the investigated neonatal risk factors.

[Anti-TNFalpha treatment of juvenile uveitis]. / Tumornekrosefaktor alpha-haemning som led i behandling af uveitis hos børn.

INTRODUCTION: To present our experience with anti-TNFalpha treatment of juvenile idiopatic arthritis (JIA) associated uveitis. MATERIALS AND METHODS: All 11 children with severe uveitis were monitored between 2001 and 2005. Nine of the children had JIA and a set of twins had a rare hereditary granulomatous disease, Blau's syndrome. The patients were selected and the reason for starting anti-TNFalpha treatment was an insufficient response in the arthritis or uveitis to previous therapy. RESULTS: In all patients the anti-TNFalpha treatment reduced the activity of uveitis. The response to treatment was related to 1) visual acuity and 2) the reduction of systemic immune-suppressing agents. All 11 children are still on anti-TNFalpha treatment. CONCLUSION: Anti-TNFalpha was effective in treating uveitis in all 11 patients. In patients with active uveitis associated JIA not responding to corticosteroids and methotrexate and with declined vision the trend is to start anti-TNFalpha treatment early in the inflammatory disease to prevent long term complications to the eyes. The results indicate a superiority of infliximab over Eternacept in the treatment of uveitis.

The prevalence and incidence of visual impairment in people of age 20-59 years in industrialized countries: a review.

BACKGROUND: Reviews on the prevalence of blindness and low vision in persons of age 20 to 59 years are lacking. We have therefore carried out a review based on a Medline search. METHODS: The review was confined to epidemiological studies performed in Western Europe, North America and Australia covering the age group 20 to 59 years where there were comparable definitions of blindness and low vision according to the IAPB and WHO classification of blindness and low vision. RESULTS: Three surveys, four register studies and two studies based on multiple sources matched our selection criteria. Blindness and low vision are described separately. Blindness: Only one study, based on multiple sources, covered the whole age group 20 to 59 years. In this study the overall prevalence of blindness was 0.08%. The prevalence of blindness was 0.04% among those 20-39 years old, whereas in the age group 40-59 years it was 0.1% in two surveys and one study on multiple sources. However, the prevalence was higher, 0.5% among whites and 0.7% among colored, in The Baltimore Eye Study. The definition of blindness was similar in all three studies. Low vision: Three studies provided data on the prevalence of low vision in the age group 20-59 years, although the number of cases was very small. In one study the prevalence of a visual acuity < or = 6/24 to 6/48 was 0.07% and in another the prevalence was 0.17% using < 6/18 to 0.5/60. No person with low vision was found in the third study. CONCLUSIONS: The existing epidemiological data on blindness and low vision among adults aged 20 to 59 years are insufficient. Epidemiological studies based on multiple sources are needed for the study of rare conditions such as blindness and low vision.