Visual outcome at 2.5 years of age in ω-3 and ω-6 long-chain polyunsaturated fatty acid supplemented preterm infants: a follow-up of a randomized controlled trial.

Background: We investigated ophthalmological outcomes at 2.5 years of corrected age in children born extremely preterm (EPT) to evaluate the effects of postnatal enteral supplementation with ω-3 and ω-6 long-chain polyunsaturated fatty acids. Methods: In the Mega Donna Mega clinical trial, EPT infants born at less than 28 weeks of gestation were randomized to receive an enteral supplementation of docosahexaenoic acid (DHA) and arachidonic acid (AA) from birth to 40 weeks postmenstrual age. In this exploratory follow-up at 2.5 years of corrected age, we assessed visual acuity (VA), refraction, manifest strabismus, and nystagmus. Satisfactory VA was defined as ≥20/63. Multiple imputation (MI) was used to address the issue of missing data. Findings: Of 178 children in the trial, 115 (with median gestational age (GA) of 25 + 4/7 weeks and median birth weights of 790 g) were ophthalmologically assessed at a median corrected age of 2.7 years (range 2.0-3.9 years). VA assessment was missing in 42.1% (75/178), in 41.7% (35/84) of the AA/DHA supplemented infants, and in 42.6% (40/94) of the control infants. After MI and adjustments for GA, study center, plurality, and corrected age at VA exam, no significant effect of AA/DHA supplementation was detected in VA outcome (≥20/63) (odds ratio 2.16, confidence interval 95% 0.99-4.69, p = 0.053). Interpretation: In this randomized controlled trial follow-up, postnatal supplementation with enteral AA/DHA to EPT children did not significantly alter VA at 2.5 years of corrected age. Due to the high loss to follow-up rate and the limited statistical power, additional studies are needed. Funding: The Swedish Medical Research Council #2020-01092, The Gothenburg Medical Society, Government grants under the ALF agreement ALFGBG-717971 and ALFGBG-971188, De Blindas Vänner, Knut and Alice Wallenberg Foundation - Wallenberg Clinical Scholars, NIHEY017017, EY030904BCHIDDRC (1U54HD090255 Massachusetts Lions Eye Foundation) supported the study.

Case report: Bilateral damage to the immature optic radiation and secondary massive loss of retinal ganglion cells causing tunnel vision.

We describe the case of a 30-year-old woman, who needed a formal report on her visual impairment to seek support from society. She was born preterm, and during her neonatal period, she suffered from bilateral intraventricular hemorrhage (IVH) grade 3, a condition that can cause cerebral visual impairment (CVI) due to damage to the retro-geniculate visual pathways. Individuals with such brain damage of this severity are often restricted by cerebral palsy (CP) and intellectual disability, and thus have a limited ability to cooperate in the assessment of visual function. However, our patient was capable of providing reliable test results, and she manifested only a small island of central vision in each eye, with additional reduced visual acuities. She cooperated well in examinations involving MRI of the brain, optical coherence tomography (OCT) of retinal ganglion cells, and multi-focal visual evoked potentials, with each test providing information about potential limitations in the structural prerequisites for visual function. What distinguishes our case is the severity of the damage to the optic radiations and the massive secondary loss of most of her retinal ganglion cells (GCs). However, there is some measurable visual function, which may be due to developmental neuroplasticity during early development, when surviving GCs prioritize the central visual field. Despite her visual difficulties, she is a keen portrait painter. Our patient may be representative of, and a spokesperson for, other individuals with extensive brain damage of the same etiology, who are unable to perform perimetric tests and therefore run the risk of not being recognized as severely visually impaired, and consequently, not being given the best conditions for habilitation. OCT may serve as a helpful diagnostic tool. Aim: This study aims to describe visual behavior and practical applications of visual function in relation to structural prerequisites for visual function.

[Survival and prematurity-related neonatal diagnoses among children born before 24 gestational weeks in Sweden 2007-2018]. / Allt fler barn födda före vecka 24 överlever, men sjukligheten är hög.

Children born before 24 gestational weeks had high neonatal morbidity and a majority had one or more neurodevelopmental disorders in addition to somatic diagnoses in childhood. Active Swedish perinatal care of infants with gestational age <24 weeks has resulted in a survival rate of more than 50 percent. Resuscitation of these immature infants is controversial, and some countries offer comfort care only. In a retrospective review of medical files and registries of 399 Swedish infants born before 24 gestational weeks, a majority had severe prematurity-related neonatal diagnoses. In childhood (2-13 years), 75 percent had at least one neurodevelopmental disorder and 88 percent had one or more prematurity-related somatic diagnosis (permanent or transient) that was likely to affect their quality of life. Long-term consequences for surviving infants should be considered in general recommendations as well as in parental information.

Retrospective evaluation of ophthalmological and neurological outcomes for infants born before 24 weeks gestational age in a Swedish cohort.

OBJECTIVES: To retrospectively evaluate ophthalmological and neurological outcomes in a Swedish cohort of infants born before 24 weeks gestational age (GA) and explore risk factors for visual impairment. SETTING: Eye and paediatric clinics in Sweden. PARTICIPANTS: Infants screened for retinopathy of prematurity (ROP) (n=399), born before 24 weeks GA, 2007-2018. Cases were excluded if ophthalmological follow-up records could not be traced. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were ophthalmological, including visual acuity (VA), refractive error, strabismus, nystagmus and cerebral visual impairment (CVI). Secondary outcomes comprised neonatal and neurological morbidities. Data were retrospectively retrieved from medical records. RESULTS: The 355 assessed children had a median GA of 23 weeks and 2 days and a median birth weight of 565 g. At the last available ophthalmological examination, the median age was 4.8 years (range 0.5-13.2 years). Nystagmus was recorded in 21.1%, strabismus in 34.8%, and 51.0% wore spectacles. Seventy-three of 333 (21.9%) were visually impaired, defined as being referred to a low vision clinic and/or having a VA less than 20/60 at 3.5 years of age or older. ROP treatment was a significant risk factor for visual impairment (OR 2.244, p=0.003). Visually impaired children, compared with children without visual impairment, more often had neurological deficits such as intellectual disability 63.8% versus 33.3% (p<0.001), epilepsy 21.1% versus 7.5% (p=0.001) and autism spectrum disorders 32.8% versus 20.9% (p=0.043). Nine of the 355 children had been diagnosed with CVI. CONCLUSIONS: Children born before 24 weeks GA frequently had visual impairment in association with neurological deficits. CVI was rarely diagnosed. A multidisciplinary approach for the evaluation and habilitation of these vulnerable infants is warranted. National follow-up guidelines need to be developed and implemented.

National cohort of infants born before 24 gestational weeks showed increased survival rates but no improvement in neonatal morbidity.

AIM: To describe survival and neonatal morbidities in infants born before 24 weeks of gestation during a 12-year period. METHODS: Data were retrieved from national registries and validated in medical files of infants born before 24 weeks of gestation 2007-2018 in Sweden. Temporal changes were evaluated. RESULTS: In 2007-2018, 282 live births were recorded at 22 weeks and 460 at 23 weeks of gestation. Survival to discharge from hospital of infants born alive at 22 and 23 weeks increased from 20% to 38% (p = 0.006) and from 45% to 67% (p < 0.001) respectively. Caesarean section increased from 12% to 22% (p = 0.038) for infants born at 22 weeks. Neonatal morbidity rates in infants alive at 40 weeks of postmenstrual age (n = 399) were unchanged except for an increase in necrotising enterocolitis from 0 to 33% (p = 0.017) in infants born at 22 weeks of gestation. Bronchopulmonary dysplasia was more common in boys than girls, 90% versus 82% (p = 0.044). The number of infants surviving to 40 weeks doubled over time. CONCLUSION: Increased survival of infants born before 24 weeks of gestation resulted in increasing numbers of very immature infants with severe neonatal morbidities likely to have a negative impact on long-term outcome.

Neurodevelopmental disorders and somatic diagnoses in a national cohort of children born before 24 weeks of gestation.

AIM: This study investigated childhood diagnoses in children born extremely preterm before 24 weeks of gestation. METHODS: Diagnoses of neurodevelopmental disorders and selected somatic diagnoses were retrospectively retrieved from national Swedish registries for children born before 24 weeks from 2007 to 2018. Their individual medical files were also examined. RESULTS: We studied 383 children born at a median of 23.3 (range 21.9-23.9) weeks, with a median birthweight of 565 (range 340-874) grams. Three-quarters (75%) had neurodevelopmental disorders, including speech disorders (52%), intellectual disabilities (40%), attention deficit hyperactivity disorder (30%), autism spectrum disorders (24%), visual impairment (22%), cerebral palsy (17%), epilepsy (10%) and hearing impairment (5%). More boys than girls born at 23 weeks had intellectual disabilities (45% vs. 27%, p < 0.01) and visual impairment (25% vs. 14%, p < 0.01). Just over half of the cohort (55%) received habilitation care. The majority (88%) had somatic diagnoses, including asthma (63%) and failure to thrive/short stature (39%). CONCLUSION: Most children born before 24 weeks had neurodevelopmental disorders and/or additional somatic diagnoses in childhood and were referred to habilitation services. Clinicians should be aware of the multiple health and developmental problems affecting these children. Resources are needed to identify their long-term support needs at an early stage.

Pre- and Postnatal Damage to the Retro-Geniculate Visual Pathways Cause Retinal Degeneration Predictive for Visual Function.

To increase the understanding of the relationship between structure and function in individuals with damage to the brain from different stages of maturation of the visual system, we examined 16 teenagers and young adults. We used diffusion-weighted magnetic resonance imaging (MRI) and fiber tractography of the optic radiation (OR) and optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell layer + inner plexiform layer (GC+IPL) in the macula. Visual field (VF) function was assessed with the Humphrey Field Analyzer (HFA). Injuries to the immature OR were associated with thinning of the pRNFL and GC+IPL, and corresponding VF defects irrespectively of timing of the lesion. However, in cases with bilateral white-matter damage of immaturity (WMDI) we noticed a well preserved central VF despite a very thin GC+IPL. We speculate that this is due to plasticity in the immature visual system. Similar results were not noticed among cases with unilateral damage, acquired pre- or postnatally, in which the central VF was affected in most cases. OCT has proved to be a valuable targeted tool in children with damage to the retro-geniculate visual pathways, and that focal thinning of the GC+IPL predicts VF defects. This brief research report includes a review of four previously published papers. In addition, we present one new case and apply a recently developed classification system for CVI. The classification was applied on cases with bilateral WMDI to investigate its relation to retinal structure.

High rate and large intercentre variability in retreatment of retinopathy of prematurity in infants born <24 gestational weeks.

OBJECTIVE: Prematurity is a major risk factor for retinopathy of prematurity (ROP). We aimed to elucidate ROP prevalence, treatment and retreatment in infants born before 24 gestational age (GA) weeks in a Swedish cohort. METHODS AND ANALYSIS: Infants with completed ROP screening, born at <24 GA weeks, 2007-2018 in Sweden were included. Data of GA, birth weight (BW), sex, neonatal morbidities, maximal ROP stage, aggressive posterior ROP (APROP), ROP treatments, treatment modality and treatment centre were retrieved. RESULTS: In total, 399 infants, with a mean GA of 23.2 weeks (range 21.9-23.9) and a mean BW of 567 g (range 340-874), were included. ROP was detected in 365 (91.5%) infants, 173 (43.4%) were treated for ROP and 68 of 173 (39.3%) were treated more than once. As the first treatment, 142 (82.0%) received laser and 29 (16.1%) received intravitreal injection of antivascular endothelial growth factor (anti-VEGF). Retreatment was performed after first laser in 46 of 142 (32.4%) and in 20 of 29 (69.0%) after first anti-VEGF treatment. Retreatment rate was not associated with GA, BW or sex but with APROP, treatment method (anti-VEGF) and treatment centre where the laser was performed (p<0.001). Twenty eyes progressed to retinal detachment, and two infants developed unilateral endophthalmitis after anti-VEGF treatment. CONCLUSION: Infants, born at <24 weeks' GA, had high rates of treatment-warranting ROP and retreatments. Treatment centre highly influenced the retreatment rate after laser indicating that laser treatment could be improved in some settings.

Severity of retinopathy of prematurity was associated with a higher risk of cerebral dysfunction in young adults born extremely preterm.

AIM: This Swedish study evaluated whether the severity of retinopathy of prematurity (ROP) in extremely preterm infants was related to their overall outcome in young adulthood. METHODS: We followed 39 individuals born between 1988 and 1993 at less than 28 gestational weeks, included in the Stockholm Neonatal Project. A total of 19 were treated for severe ROP, and 20 had no or mild ROP. They were assessed for general cognitive abilities and mental health at 18 years of age and compared with 23 term-born controls. Visual acuity was examined at 21-25 years. They were asked about their education and everyday life. RESULTS: The 19 individuals with severe treated ROP had lower visual acuity and higher risk for intellectual deficits, cerebral palsy and neuropsychiatric diagnoses than those with no or mild ROP and the term controls. Three were visually impaired, none were blind. They were less physically active than the other groups and had more problems finding their way around. However, nine were at university. CONCLUSION: Young adults treated for severe ROP had more problems resulting from cerebral dysfunction than those with no or mild ROP and term-born controls. Retinal and brain pathologies in the extremely preterm infant constitute different expressions of neurovascular disease.

Economic consequences of migraine in Sweden and implications for the cost-effectiveness of onabotulinumtoxinA (Botox) for chronic migraine in Sweden and Norway.

BACKGROUND: Migraine is a common and incapacitating condition, with severe impact on the quality of life (QoL) of the afflicted and their families, and negative economic consequences through decreased workforce participation, reduced functional ability and elevated healthcare costs. This study aimed to describe the economic consequences of migraine in Sweden using cost of illness survey data and, based on this data, assess the cost-effectiveness of onabotulinumtoxinA (Botox) for the treatment of chronic migraine in Sweden and Norway. METHODS: A survey study was conducted in Swedish migraine patients, with questions on patient characteristics, headache frequency and severity, effect on daily activities and work, QoL, health resource utilization, and medication use. Resulting costs were estimated as annual averages over subgroups of average monthly headache days. Some results were used to inform a Markov cost-effectiveness chronic migraine model. The model was adapted to Sweden and Norway using local data. The analysis perspective was semi-societal. Results' robustness was tested using one-way, structural, and probabilistic sensitivity analyses. RESULTS: Results from the cost of illness analysis (n = 454) indicated a clear correlation between decreased QoL and increased costs with increasing monthly headache days. Total annual costs ranged from EUR 6221 in patients with 0-4 headache days per month, to EUR 57,832 in patients with 25-31. Indirect costs made up the majority of costs, ranging from 82% of total costs in the 0-4 headache days group, to 91% in 25-31 headache days. The cost-effectiveness analyses indicated that in Sweden, Botox was associated with 0.223 additional QALYs at an additional cost of EUR 4126 compared to placebo, resulting in an incremental cost-effectiveness ratio (ICER) of EUR 18,506. In Norway, Botox was associated with 0.216 additional QALYs at an additional cost of EUR 4301 compared to placebo, resulting in an ICER of EUR 19,954. CONCLUSIONS: In people with migraine, an increase in monthly headache days is clearly related to lower QoL and higher costs, indicating considerable potential costs-savings in reducing the number of headache days. The main cost driver for migraine is indirect costs. Botox reduces headache days and is a cost-effective treatment for chronic migraine in Sweden and Norway.

Retinal ganglion cell topography predicts visual field function in spastic cerebral palsy.

The aim of this study was to evaluate the use of optical coherence tomography (OCT) to identify and assess visual field defects caused by primary damage to the optic radiation in individuals with spastic cerebral palsy (CP). Ten individuals with spastic CP (six females, four males, with a median age of 21 years [range 17-38y]) had their brain lesions documented with conventional magnetic resonance imaging (MRI) and diffusion-weighted MRI fibre tractography. Their macular ganglion cell layer (GCL) and inner plexiform layer (IPL) were examined with OCT and their visual fields were plotted. All participants had good visual acuity and were able to cooperate with the MRI and OCT examinations, as well as undergoing reliable perimetry. We found focal thinning of the GCL+IPL and corresponding homonymous visual field defects in individuals with brain damage affecting the optic radiation. We used GCL+IPL sector asymmetry as a sensitive OCT parameter to identify focal visual field defects. We observed no such sector asymmetry in GCL+IPL, or focal visual field defects, in individuals with normal MRI optic radiation imaging. Lesions affecting the optic radiation cause retrograde trans-synaptic degeneration of retinal ganglion cells. OCT examination of the GCL in the macula identified corresponding focal damage to the optic radiation in individuals with spastic CP and can be used to predict focal visual field defects. WHAT THIS PAPER ADDS: Spastic cerebral palsy (CP) may be associated with damage to the optic radiation. Damage to the optic radiation causes retrograde trans-synaptic degeneration (RTSD). RTSD can be mapped using optical coherence tomography. Ganglion cell topography can predict visual field defects in individuals with spastic CP.

Cerebral visual impairment captured with a structured history inventory in extremely preterm born children aged 6.5 years.

PURPOSE: To investigate whether a questionnaire can identify cerebral visual impairment (CVI) in a group of 6.5-year-old children born extremely preterm (EPT) as accurately as direct assessments. METHODS: This prospective population-based study included 120 children born before 27 weeks' gestational age (66 males; mean, 25.4 ± 1.0 weeks) and 97 full-term controls (56 males; mean, 39.9 ± 1.1 weeks) at the age of 6.5 years, as part of the Extremely Preterm Infants in Sweden Study (EXPRESS). A questionnaire for detection of CVI was evaluated and compared with visual, perceptual, and cognitive assessments. RESULTS: Parents of children born EPT reported more CVI features than the parents of control children, with median sum scores of 25 (95% CI, 18.1-31.9) and 11 (95% CI, 8.8-13.2), respectively (P < 0.001), and a median difference of 14 (95% CI, 6.6-21.4). Low rates of reported CVI features were significantly associated with better results from direct assessments within the EPT group and with less pronounced differences compared to controls. CONCLUSIONS: The questionnaire discriminated well between children born EPT and controls, and the scores were congruent with other evidence of visual, perceptual, and cognitive deficits. The easily used questionnaire compared favorably with direct assessment in identifying CVI in children born EPT and also provides valuable information to clinicians, and parents about the daily life problems associated with CVI.

Ganglion Cell Topography Indicates Pre- or Postnatal Damage to the Retro-Geniculate Visual System, Predicts Visual Field Function and May Identify Cerebral Visual Impairment in Children - A Multiple Case Study.

In this paper, we quantify the degree of ganglion cell layer thinning due to retrograde trans-synaptic degeneration (RTSD) from retro-geniculate damage in six cases who had homonymous visual field defects known since childhood. Three had prenatal injuries, occurring close to mid-gestation and in the first parts of the early and late third trimester, respectively, and representing injuries at different early developmental stages. Three had later acquired injuries, at age 1.5, 4 and 13 years. The impact of the injury to the optic radiations was revealed by fibre tractography. The ganglion cell thinning corresponded with the visual field defects and the extent and location of the primary brain damage. The most important sign of RTSD was asymmetry of the ganglion cell topography within the macular area.

Injuries to the Immature Optic Radiation Show Correlated Thinning of the Macular Ganglion Cell Layer.

Injuries to the immature optic radiation (OR) are associated with thinning of the retinal nerve fiber layer and corresponding visual field (VF) defects. The aim of the current study was to seek evidence for causal retrograde trans-synaptic degeneration by exploring the correspondence between the localization and extension of the injury to the OR and the structure of the macular ganglion cell complex, and the relation to VF function. Seven adults (age range 18-35) with visual dysfunction secondary to white-matter damage of immaturity and six healthy adults (age range 22-33) underwent magnetic resonance imaging (MRI). Fiber tractography was used to generate the geniculate projections to the dorsal and ventral striate cortex, delineated by retinotopic functional MRI mapping. The structure of the macular ganglion cell complex was measured with optical coherence tomography. The tractography showed overlaps between the dorsal and ventral geniculo-striate projections. However, in four patients with inferior VF defects, the dorsal projections were to a large extent traversing the space normally solely occupied by ventral projections. This is consistent with structural changes to the OR and suggests of re-organization upon injury. Diffusion parameters were significantly different between patients and controls, and most pronounced in the dorsal geniculo-striate projections, with a pattern indicating primary injury. The macular ganglion cell complex was significantly thinner in the patients and most pronounced in the superior sectors; a pattern particularly evident in the four patients with inferior VF defects. The ratio of the mean thickness of the macular ganglion cell complex in the superior and inferior sectors significantly correlated with the axial and mean diffusivities in the contra- and ipsilateral dorsal striate projections. The results suggest a causal link between injuries to the superior portion of the immature OR and secondary thinning in the macular ganglion cell complex, resulting in inferior VF defects.

Motion Perception and Form Discrimination in Extremely Preterm School-Aged Children.

This population-based study evaluated motion and form perception in 71 children born extreme premature (EPT; < 27 gestational weeks), aged 6.5 years, as compared to a matched group of 79 control children born at term. Motion and form perception were evaluated by motion coherence and form coherence tests. The EPT group showed a poorer performance on both tasks as compared to the control group. However, after controlling for IQ and visual acuity, the EPT group showed only a significant deficit in motion perception. No association was found between motion perception accuracy and gestational age, previous retinopathy of prematurity, or previous intraventricular hemorrhage in the EPT group. The results highlight the long-term motion perception deficits in children born EPT.

Retinopathy of Prematurity Is Associated with Increased Systolic Blood Pressure in Adults Who Were Born Preterm.

BACKGROUND: Adults born preterm are at risk of developing cardiovascular morbidities. OBJECTIVE: The aim of this study was to evaluate the relationship between retinopathy of prematurity (ROP) and blood pressure (BP) and salivary cortisol levels during adulthood. METHODS: Sixty-nine subjects (mean age 22.6 years) were included. Subjects were adults who were: (a) ex-preterm infants with severe ROP (n = 22), born at gestational age (GA) <30 weeks with a birth weight (BW) <1,000 g, (b) ex-preterm infants with no/mild ROP (n = 21), born at GA <28 weeks with a BW <1,000 g, or (c) full-term controls (n = 26). Anthropometric data, office BP, ambulatory BP, and morning and evening salivary cortisol were analyzed. RESULTS: As adults, ex-preterm infants with severe ROP had on average 7.4 mm Hg higher systolic office BP than those with no/mild ROP (p = 0.019) and controls (p = 0.007). A high cortisol level, tall height, and severe ROP were independent predictors of higher ambulatory systolic BP during adulthood in forward stepwise regression analysis, independent of GA. CONCLUSION: Our results indicate that preterm infants with severe abnormal retinal vascular development during the neonatal period may be at an increased risk for increased BP during adulthood. We found no differences between those with no/mild ROP as infants and controls with regard to BP data.

Retinal Sequelae in Adults Treated With Cryotherapy for Retinopathy of Prematurity.

PURPOSE: Cryotherapy, introduced in the mid-1980s, was the first treatment of severe retinopathy of prematurity (ROP) and resulted in ablation of larger retinal areas than did its later substitute, laser treatment. We defined the characteristics of the retinal structure and assessed visual function, in adult ex-preterms treated with cryotherapy. METHODS: A total of 28 ex-preterms, included in a prospective study of infants born in Stockholm between September 1988 and March 1993, were treated with cryotherapy because of severe ROP. Of these individuals, 14 took part in this follow-up study and underwent ophthalmologic assessment including visual acuity, fundus photography, perimetry, and retinal imaging using optical coherence tomography (OCT) in their third decade of life. Their gestational ages were 24 to 28 (median 25) weeks at birth. RESULTS: The ex-preterms had reduced foveal depth (P < 0.0001) and increased thickness of the temporal retinal nerve fiber layer (RNFL; P > 0.001). A thicker temporal RNFL was not correlated with a thicker ganglion cell layer (P = 0.41, r = 0.29) as in controls (P = 0.0015, r = 0.78). Extreme thickening was seen in patients with pronounced retinal dragging. CONCLUSIONS: In their third decade of life, ex-preterm adults treated with cryotherapy for ROP have major microstructural retinal abnormalities in terms of reduced foveal depth and an altered distribution of the peripapillary RNFL. The main contributors seem to be gestational age and ROP rather than the cryotherapy. The possibility to evaluate the retinal structure in these individuals, with today's conventional OCT, is limited by those anatomic deviations.

Damage to the immature optic radiation causes severe reduction of the retinal nerve fiber layer, resulting in predictable visual field defects.

PURPOSE: The aim of the present study was to seek evidence of a relationship between damage to the optic radiation (OR) in the immature brain and subsequent development of the retinal nerve fiber layer (RNFL) and associated visual manifestations. METHODS: Seven cases (2 males and 5 females ranging in age from 18 to 35 years old) were selected from a large cohort of individuals with known white matter damage of immaturity (WMDI), who had presented with visual dysfunction. They underwent magnetic resonance imaging (MRI), including diffusion-weighted MRI. Visual function was evaluated by best-corrected visual acuity and visual field (VF) testing using Goldmann perimetry and Humphrey field analyzer (HFA). RNFL thickness was measured by optical coherence tomography. RESULTS: A homogeneous lesion pattern with bilateral WMDI predominantly in the superior posterior periventricular white matter was seen in all subjects. However, as shown by white matter fiber tractography, only cases with injuries to the superior portion of the OR had corresponding inferior VF defects. In the individuals showing structural abnormalities in the OR, a commensurate reduction in the peripapillary RNFL was seen. The RNFL loss was most pronounced in the subjects suffering from the more extensive lesions, and it followed the pattern of OR damage in the sense that damage in the superior portion of the OR gave a reduced RNFL thickness in the superior part of the peripapillary RNFL. CONCLUSIONS: Primary injuries in the immature OR are associated with reduced RNFL thickness, and examination of the RNFL may be a helpful predictor of VF defects.

Cost-effectiveness of apixaban versus warfarin and aspirin in Sweden for stroke prevention in patients with atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF), one of the major risk factors for stroke, imposing a substantial burden to the Swedish health care system. Apixaban has demonstrated superiority to warfarin and aspirin in stroke prevention amongst patients with AF in two large randomised clinical trials. The aim of this study was to assess the economic implications of apixaban against warfarin and aspirin in these patients from a Swedish societal perspective. MATERIALS AND METHODS: A Markov cohort model was constructed to characterise the consequences of anticoagulant treatment with regards to thromboembolic and bleeding events, as well as the associated health care costs, life-years and quality-adjusted life years (QALYs) for patients with AF treated with apixaban, warfarin or aspirin. Incremental cost-effectiveness ratios (ICERs) per QALY gained of apixaban relative to warfarin (among patients suitable for warfarin treatment) and aspirin (among patients unsuitable for warfarin treatment) were calculated. Costs (in 2011 SEKs) and QALYs were discounted at 3% per annum. RESULTS: The model estimated the ICER of apixaban versus warfarin amongst patients who are suitable for warfarin therapy to be SEK 33,458/QALY gained and that of apixaban versus aspirin amongst those unsuitable for warfarin therapy to be SEK 41,453/QALY gained. Probabilistic sensitivity analyses indicate that apixaban is an optimal treatment option compared with warfarin and aspirin, when the willingness-to-pay is above SEK 35,000 and SEK 45,000 per QALY, respectively. CONCLUSIONS: Apixaban was found to be a cost-effective alternative to warfarin and aspirin for stroke prevention in patients with AF in Sweden.