The genetic aetiology of retinal degeneration in children in Finland - new founder mutations identified.

PURPOSE: To study the genetic aetiology and phenotypes of retinal degeneration (RD) in Finnish children born during 1993-2009. METHODS: Children with retinal degeneration (N = 68) were investigated during 2012-2014 with a targeted gene analysis or a next-generation sequencing (NGS) based gene panel. Also, a full clinical ophthalmological examination was performed. RESULTS: The cohort covered 44% (68/153) of the Finnish children with inherited RD born 1993-2009. X-linked retinoschisis, retinitis pigmentosa, Leber congenital amaurosis and cone-rod dystrophy were the most common clinical diagnoses in the study group. Pathogenic mutations were found in 17 retinal genes. The molecular genetic aetiology was identified in 77% of the patients (in 77% of the families) analysed by NGS method. Several founder mutations were detected including three novel founder mutations c.148delG in TULP1, c.2314C>R (p.Gln772Ter) in RPGRIP1 and c.533G>A (Trp178Ter) in TYR. We also confirmed the previous tentative finding of c.2944 + 1delG in GYCU2D being the most frequent cause of Leber congenital amaurosis (LCA) in Finland. CONCLUSIONS: Globally, RD is genetically heterogeneous with over 260 disease genes reported so far. This was shown not to be the case in Finland, where the genetic aetiology of RD is caused by a small group of genes, due to several founder mutations that are enriched in the population. We found that X-chromosomal retinoschisis constitutes the major group in Finnish paediatric RD population and is almost exclusively caused by two founder mutations. Several other founder mutations were detected including three novel founder mutations. All in all, the genetic aetiology of 77% of families was identified which is higher than previously reported from other populations, likely due to the specific genomic constitution of the Finns.

Improving visual prognosis of the diabetic patients during the past 30 years based on the data of the Finnish Register of Visual Impairment.

PURPOSE: To evaluate changes in visual impairment (VI) due to diabetic retinopathy (DR) recorded in the Finnish Register of Visual Impairment (RVI) during the past 30 years. METHODS: Data from the visually impaired diabetic persons included in the RVI were analysed using three 10-year cohorts (1982-90, 1991-2000, 2001-10). Information on the age at the time of the first VI registration, severity of VI determined according to the World Health Organisation (WHO) definition, and the age at death was collected. VI due to proliferative (PDR) and non-proliferative (NPDR) DR were analysed separately. RESULTS: Data of 4080 patients whose primary cause for VI was DR were analysed. The median age at the time of notification of VI for the three cohorts was 39, 62 and 59 years in the PDR group and 71, 73 and 73 in the NPDR group, respectively. The proportion of blind persons was 42%, 22% and 15% in the PDR group and 10%, 9% and 4% in the NPDR group, respectively. The median age at death in the three cohorts was 54, 73 and 72 years in PDR group and 76, 79 and 80 years in the NPDR group, respectively. The standardized mortality ratio (SMR) compared with the general population was 8.3, 2.9 and 1.4 in persons with PDR and 3.4, 2.0 and 1.2 in those with NPDR, respectively. CONCLUSIONS: A significant change in the profile of the VI in the PDR group has taken place in Finland. It was characterized by increased age at the time of VI notification, decreased severity of VI and higher age at death. Most evidently these improvements took place in the 1990s. The profile of VI in the NPDR group has changed only modestly. Compared with the general population, SMRs improved both in NPDR and PDR groups continuously.

Use of eye care services and need for assistance in the visually impaired.

PURPOSE: To assess the use of eye care services and unmet need for assistance in visually impaired people. METHODS: Cross-sectional population-based survey on a sample representing the Finnish population aged 30 years and older. Of the 7979 eligible people, 6645 (83.3%) were both interviewed and had their distance visual acuity (VA) assessed. One hundred forty-seven people were classified as visually impaired (VA < or = 0.25). A home interview included an assessment of the use of eye care services, need for assistance, sociodemographic variables, cognitive functioning, and mobility. Binocular VA for distance was measured with the participants' current spectacles, if any, as a part of a comprehensive health examination. RESULTS: One-half (58%) of visually impaired people had had a recent vision examination and 79% had received some vision rehabilitation services, mainly in form of spectacles (70%). Only one third (31%) had received formal low vision rehabilitation. People with moderate visual impairment (VA 0.1 to 0.25) were less likely to have received low vision rehabilitation, magnifying glasses, or other low vision aids compared with people with severe low vision (VA < 0.1). Furthermore, low cognitive capacity and living in an institution were associated with limited use of vision rehabilitation services. Of the visually impaired people living in the community, 71% reported need for assistance and 24% of them had unmet need for assistance in everyday activities. Although need for assistance was more common in people with severe low vision (83% vs. 67%, p = 0.09), unmet need for assistance seemed to be more common in people with moderate low vision (20% vs. 9%, p = 0.23). CONCLUSIONS: Many visually impaired people, older persons in particular, have not had a recent vision examination and lack adequate low vision rehabilitation. This highlights the need for regular evaluation of vision function in elderly people and for actively supplying information about rehabilitation services.

The association between visual acuity and functional limitations: findings from a nationally representative population survey.

PURPOSE: To determine the independent effect of visual acuity on individual activities of daily living (ADL), instrumental activities of daily living (IADL) and mobility. METHODS: Cross-sectional survey on a sample representing the Finnish population aged 55 years and above. Of the 3392 eligible people, 3185 (93.9%) were interviewed, 2870 (84.6%) attended a comprehensive health examination, and 2781 (82.0%) had distance visual acuity (VA) assessed. A home interview included assessment of ADL, IADL and mobility, demographic variables and chronic conditions. Mobility measurements and binocular VA were assessed during the examination. RESULTS: Prevalence of ADL, IADL, and mobility limitations increased with decreasing VA (p<0.001). Visually impaired persons (VA< or =0.25) had ADL disabilities four times more likely than those with good VA (VA> or =0.8) after adjustment for socio-demographic and behavioral factors, and chronic conditions (OR 4.36, 95%CI 2.44-7.78). Limitations in IADL and measured mobility were five times as likely (OR 4.82, 95%CI 2.38-9.76 and OR 5.37, 95%CI 2.44-7.78, respectively), and self-reported mobility limitations were three times as likely (OR 3.07, 95%CI 1.67-9.63) as in persons with good VA. CONCLUSIONS: Decreased VA is strongly associated with functional limitations, and even a slight decrease in VA was found to be associated with limitations in functioning.

Does incidence of breast cancer and prostate cancer decrease with increasing degree of visual impairment.

OBJECTIVE: The issue of light at night and cancer continuously attracts discussion. The major hypotheses are that melatonin may decrease risk of hormone-related cancers, particularly breast cancer, or even act as a potent antioxidant and thus have a protective effect against cancer development in general. METHODS: We tested the hypothesis that blind persons are at lower risk of cancer in a follow-up study linking a cohort of 17,557 persons with visual impairment identified from the Finnish Register of Visual Impairment with cancer incidence data of the Finnish Cancer Registry for years 1983-2003. RESULTS: Breast cancer risk in females decreased by degree of visual impairment, and a similar but less consistent trend was observed for prostate cancer in males. The incidence for the remaining cancers among nearly to totally blind persons was significantly higher than in average Finnish population. CONCLUSIONS: Our findings add to the suggestive epidemiological evidence for a decreased risk of hormone-related cancers in people with visual impairment and, consequently, a relationship between visible light at night and breast cancer risk. The result is strongly against the hypothesis of a systemic protective effect related lack of visible light.

Visual impairment in children born at full term from 1972 through 1989 in Finland.

OBJECTIVE: To investigate the incidence, prevalence, and causes of visual impairment in children born at full term and to determine conditions and factors associated with visual impairment. DESIGN: Retrospective, cross-sectional, population-based study. PARTICIPANTS: All visually impaired individuals from 0 to 17 years of age who were born at full term from 1972 through 1989 in Finland and recorded in the Finnish Register of Visual Impairment (n = 556) were eligible for this study. METHODS: Data in the Finnish Register of Visual Impairment relating to 556 subjects were supplemented with data from hospital records and other national registers (Register of Births, Register of Congenital Malformations, Finnish Care Register, and Finnish Cancer Register). Data relating to the children born at full term were compared with Finnish perinatal and vital statistics and with data concerning children born prematurely. The chi-square test (Mantel-Haenszel) and stepwise logistic regression analysis were used in statistical analysis of the data. MAIN OUTCOME MEASURES: Visual acuity, time of onset of visual impairment, ophthalmic diagnosis of visual impairment, systemic disease, multiple handicap, 5-minute Apgar score, prenatal disorders, perinatal disorders, disorders arising during infancy and childhood, and treatment. RESULTS: Four hundred thirty-one of the 556 individuals with visual impairment (78%) had been born at full term. Visual impairment was predominantly associated with genetic (53%) and prenatal (34%) factors. Ocular malformations (34%), retinal diseases (31%), and neuro-ophthalmologic disorders (26%) were the main ophthalmic diagnoses. Optic nerve atrophy (20%) and congenital cataract (13%) were the most common single diagnoses. The occurrence of blindness, systemic disease, and multiple handicap was 40%, 43%, and 45%, respectively. CONCLUSIONS: The incidence of visual impairment in children born at full term did not decline during the 2 decades covered by this study. The findings reflected the lack of treatment for genetic eye diseases. The results also confirmed an obvious need for further understanding of mechanisms underlying congenital anomalies of the human visual system.

Visual impairment in children born prematurely from 1972 through 1989.

PURPOSE: To investigate the incidence and causes of visual impairment in children born prematurely in Finland from 1972 through 1989, and to determine what conditions and factors were associated with its occurrence. DESIGN: Retrospective, cross-sectional study. SUBJECTS: All visually impaired individuals from 0 to 17 years of age who had been born at fewer than 37 gestational weeks in Finland from 1972 through 1989 for whom records were available in the Finnish Register of Visual Impairment were eligible for this study. METHODS: Data in the Finnish Register of Visual Impairment relating to 556 children were supplemented with data from hospital records, and from the Register of Births, the Register of Congenital Malformations, the Finnish Care Register, and the Finnish Cancer Register. Data relating to causes associated with visual impairment in particular were collected. Data relating to the children born prematurely were compared with data relating to children born at full term. The chi-square test (Mantel-Haenszel), the Mann-Whitney U test, Fisher exact test, and stepwise logistic regression analysis were used in statistical analysis of the data. MAIN OUTCOME MEASURES: Visual acuity, ophthalmologic diagnoses, associated systemic disease, multiple handicap, gestational age, birth weight, 5-minute Apgar scores, and prenatal, perinatal, and infantile or juvenile disorders or disease and treatment. RESULTS: One hundred twenty-five of the 556 visually impaired children (23%; 11/100000 children less than 18 years of age) had been born preterm. Retinopathy of prematurity, optic atrophy, and cerebral amblyopia were the main diagnoses associated with visual impairment (in 46%, 28%, and 12% of cases, respectively). Sixty-six percent of those born prematurely with visual impairment were also affected by other handicaps (mental, motor, auditory), 54% by cerebral palsy and 36% by epilepsy. Eighty-eight of the 125 children (70%) born preterm with visual impairment were blind. Very low birth weight (<1500 g), young gestational age (fewer than 30 weeks), prenatal infection, hyperbilirubinemia, respiratory disorders, asphyxia, and lengthy mechanical ventilation were associated with an increased risk of visual impairment. CONCLUSIONS: Premature birth was a major risk factor of severe visual impairment and blindness in childhood. The visual impairment often was accompanied by cerebral palsy, epilepsy, and other motor and mental handicaps. Retinopathy of prematurity, optic atrophy, and cerebral amblyopia were the main diagnoses associated with visual impairment. During the 18 years covered by the study, the increasing incidence of survival of infants born weighing fewer than 1500 g was associated with increasing incidence of blindness.