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.

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.

Profound bilateral visual loss after hysterectomy indicated for severe postpartum haemorrhage.

We present a case of a patient with bilateral posterior ischaemic optic neuropathy in the previously unreported setting of hysterectomy indicated for severe postpartum haemorrhage. The diagnosis was based on clinical and paraclinical examinations, including MRI of the head, electroretinography (ERG) and visual evoked potentials (VEP) testing. During 1 year of follow-up, repeated optical coherence tomography (OCT) scans demonstrated optic disc atrophy, which was interpreted as a sign of direct retrograde ganglion cell degeneration after ischaemic damage to the retrolaminar part of the optic nerves. The diagnosis of perioperative posterior ischaemic optic neuropathy is mostly a clinical diagnosis. However, MRI plays a major role in excluding other causes of visual loss, and VEP, ERG and OCT are valuable supplemental diagnostic tools.

Photoreceptor atrophy in acute zonal occult outer retinopathy.

PURPOSE: To assess retinal morphology in acute zonal occult outer retinopathy (AZOOR) without ophthalmoscopically visible fundus changes. METHODS: Retrospective case series. Two consecutive patients with bilateral AZOOR with photopsia corresponding to areas of visual field loss and a normal fundus appearance were examined using optical coherence tomography (OCT), automated perimetry and electroretinography (ERG). RESULTS: Both patients demonstrated photoreceptor atrophy corresponding to partial or complete scotomata with reduced or extinct electroretinographic responses. Attenuation or complete loss of all the segments composing the photoreceptor layer was found by OCT. Full-field ERG revealed affection of the 30 Hz flicker responses and subnormal photopic responses in both patients and subnormal scotopic responses in case 1. Multifocal electroretinography (mERG) revealed localized outer retinal dysfunction. The field loss was more extensive than the area of photoreceptor loss. CONCLUSION: Photoreceptor atrophy can be demonstrated in AZOOR without ophthalmoscopically visible fundus lesions.

Sequels of Purtscher's retinopathy imaged by enhanced optical coherence tomography.

PURPOSE: To report the optical coherence tomography (OCT) findings in a case of Purtscher's retinopathy. METHODS: Enhanced optical coherence tomography, fundus photography, multifocal electroretinography. RESULTS: A 27-years-old female parachutist demonstrated outer retinal opacification with small intraretinal hemorrhages and corresponding binocular pericentric ring scotomata one day after suffering an unusually abrupt arrest of a free fall upon the unfolding of her parachute. When seen 20 years later, the scotomata were unchanged and optical coherence tomography showed bilateral disorganization at the transition between the retinal photoreceptor outer segments and the retinal pigment epithelium plus attenuation of the outer nuclear layer. CONCLUSIONS: Our observations document that the long term sequels of Purtscher's retinopathy are located in the outer segments of the photoreceptors.