Primary congenital glaucoma in Denmark, 1977-2016.

PURPOSE: To perform an epidemiological survey of all patients in Denmark diagnosed with primary congenital glaucoma (PCG) from 1977 to 2016. METHODS: A retrospective, nationwide study based on a review of medical files of all children with PCG born in Denmark from 1977 to 2016. PCG was defined as glaucoma due to isolated angle dysgenesis affecting children from birth and including late onset/late recognized PCG, excluding glaucoma associated with other congenital abnormalities. Incidence and risk factors of PCG including gender, consanguinity, family history, ethnicity, comorbidity and prematurity were evaluated and stratified by decade (1977-1986, 1987-1996, 1997-2006 and 2007-2016). Age at first symptoms, age at diagnosis, age at time of first surgery and possible diagnostic delay were assessed. RESULTS: Of 118 patients were identified, annual incidence of PCG was 4.8 per 100 000 live born. 62.3% of cases were bilateral. The relative risk (RR) of PCG was significantly higher in boys (62.7% of patients, RR 1.60 (95% CI 1.10-2.32)). 13.6% had comorbidity. Median age at time of first symptoms was 75 days, median age at time of diagnosis was 150 days and median diagnostic delay was 75 days with no significant difference throughout the decades. Unilateral cases presented symptoms and were diagnosed significantly later than bilateral cases. CONCLUSION: We provide unique nation-based information on the incidence of PCG from a single country covering 40 years. Male gender was a risk factor. Diagnostic delay was unchanged throughout the 4 decades and a high percentage of comorbidity was revealed. Introducing a standardized paediatric screening of all PCG children should be considered.

[Ocular torticollis is a diagnostic and surgical challenge].

Torticollis is an abnormal head posture caused by ocular or non-ocular factors. Ocular torticollis (OT) is a compensatory head posture adopted to avoid double vision or dampen nystagmus. In this review, we argue, that causes for OT comprise a wide range of congenital or acquired ocular conditions. These patients are at risk of being mis-cat-egorised as having non-ocular torticollis, which may delay treatment and cause amblyopia in children. OT can be symptomatically relieved by prismatic correction incorporated in the patient's glasses or treated by strabismus surgery, which also improve ocular motility.

Analysis of the current preschool vision screening in Denmark.

PURPOSE: To analyse the current vision screening programme for children attending school with respect to identifying children with significant refractive errors. METHODS: A total of 950 children from the municipality of Roskilde, Denmark, were invited to participate in a cross-sectional study of vision screening. 447 children aged 4.5-7 years participated in the study. The children completed a vision screening and a full eye examination. The vision screening consisted of visual acuity at distance (VA), visual acuity at distance with +2.0 glasses (VA+2), visual acuity at near (VAnear) and Lang II stereotest. A LogMAR-based picture chart was used for the vision testing. Significant refractive errors were defined as hyperopia ≥+3.5 D, myopia >1.0 D, astigmatism ≥1.25 D and anisometropia >1.0 D. RESULTS: Using receiver operating characteristic (ROC) curves, we could compare the efficiency of VA, VA+2, VAnear, VA in combination with VA+2 and VA in combination with VAnear. Area under the curve (AUC) for VA, VA combined with VA+2 and VA combined with VAnear was 0.841, 0.857 and 0.857, respectively, that is all classified as 'very good' screening tools, whereas VA+2 and VAnear as single screening tools were classified as 'good' with AUC of 0.704 and 0.775, respectively. Using the optimal cut-off limit from the ROC curves, VA above 0.05 LogMAR as cut-off limit showed a sensitivity of 85.2% with a specificity of 74.9%. A slightly higher sensitivity could be found when combining screening tests, but with declining specificities. CONCLUSION: Visual acuity at distance with the use of LogMAR-based charts is the optimal screening tool of choice; only minor improvements can be obtained combining with other tests.

Ophthalmological data on 4.5- to 7-year-old Danish children.

PURPOSE: To report normative data on visual acuity (VA) for near and distance, refraction, ocular alignment, ocular motility and stereo acuity in a cohort of children aged 4.5-7 years. METHODS: A total of 950 children with normal development from the municipality of Roskilde, Denmark, were invited to participate in an ophthalmic cross-sectional population-based survey, of which 445 children in the age of 54-87 months participated with a complete ocular examination including cycloplegia. Visual acuity (VA) was tested using Kay Picture charts and notified in logMAR units. RESULTS: Mean distance VA was 0.010 logMAR [standard deviation (SD): 0.048] in right eye, and near VA in right eye was 0.012 logMAR (SD: 0.054), with a nonsignificant difference between right and left eye in both parameters (paired t-test, p = 0.15 and p = 0.08, respectively). Amblyopia was found in 12 children (2.7%), mainly related to refractive errors. The mean refractive error of right eye was +1.75 D, and significant hyperopia (greater than +3.0 D) was found in 7.9%. No myopia (greater than or equal to -0.5 D) was found, astigmatism (>1 D) was seen in 4.3%. Manifest strabismus was present in 1.6%, and heterophoria in 4.0%. Reduced or absent stereo acuity was present in 35 children (7.9%) and was related to a reduced VA, refractive error and strabismus. CONCLUSION: Ophthalmic data of 445 normally developed children are presented, supplementing previous reported normative data in children. We found a relatively high prevalence of amblyopia and of hyperopia, while myopia was not found, confirming previous studies that myopia is not developing at early age in Danish children.

CYP1B1 Mutations in Individuals With Primary Congenital Glaucoma and Residing in Denmark.

PURPOSE OF THE STUDY: Primary congenital glaucoma (PCG OMIM 231300) can be caused by pathogenic sequence variations in cytochrome P450, subfamily 1, polypeptide 1 (CYP1B1). The purpose of this study was to investigate the contribution of sequence variations in CYP1B1 in a cohort of individuals with PCG residing in Denmark. METHODS: The study included 37 unrelated individuals with PCG. Individuals were investigated for CYP1B1 mutations by Sanger sequencing of polymerase chain reaction products using BigDye terminators and capillary electrophoresis. RESULTS: A total of 12 mutations were identified and 5 of these were novel. Six were missense mutations; 4 were truncating mutations (2 nonsense and 2 frameshift); 1 was an in-frame deletion and 1 was an in-frame duplication. Mutations in CYP1B1 could fully explain the PCG phenotype in 7 individuals (18%). Five individuals were compound heterozygous or presumed compound heterozygous, 1 was homozygous and 1 was apparently homozygous. Three individuals were heterozygous for sequence variations in CYP1B1 thought to be pathogenic-one of these was p.(Tyr81Asn). Several known sequence variations with presumably no functional effect were found in the cohort. CONCLUSIONS: In this study, we identified 12 CYP1B1 mutations, 5 of which were novel. The frequency of CYP1B1 mutations in this cohort was comparable with other populations. We also detected an individual heterozygous for p.(Tyr81Asn) mutation, previously suggested to cause autosomal dominant primary open-angle glaucoma.

Ophthalmic experience over 10 years in an observational nationwide Danish cohort of Fabry patients with access to enzyme replacement.

PURPOSE: Enzyme replacement therapy (ERT) was offered from year 2001 to patients with Fabry disease. The ophthalmic experience was analysed, as part of a general 10-year status. METHODS: A retrospective observational series comprising 39 patients (25 females, 14 males) closely followed by the endocrinologists, and with regular ophthalmic control. Time of inclusion was when the option of ERT was started, at age 11-60 years. Eye data (standard eye examination, including retinal imaging) were incomplete in five, due to death or non-attendance, and five patients had refused treatment. RESULTS: Vision was normal throughout, except in two young males with total unilateral central retinal artery occlusion, prior to and during enzyme replacement, respectively. Cornea verticillata and conjunctival vessel ectasies were common. Tortuosity of retinal arterioles and venules was recorded in eight and 18 patients, respectively, and phlebopathy in 22, although generally without evidence of loss of vessel wall integrity. Systemic vascular lesions with or without loss of function were recorded for kidney (n = 23), heart (n = 17) and brain (n = 7), and an association was suggested between nephropathy and abnormal morphology of retinal vessels. CONCLUSIONS: Thirteen of 32 patients on ERT showed a reduction of corneal deposits over the study period. Abnormal ocular vessel morphology was a frequent finding. In contrast to the function loss related to systemic ischaemic lesions, we found no indication of impairment of visual parameters in 37. Compared to other Fabry series, two of 39 patients with serious unilateral occlusive retinal disease may appear a high number. The presence of retinal tortuosity is discussed, possibly reflecting haemodynamic events related to vessel wall deposits, but could also be 'constitutional', as part of the Fabry inheritance.