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PurposeThe aim of this study was to examine the cerebrospinal fluid (CSF) flow rates in the subarachnoid space (SAS) of the optic nerve (ON) and the brain in patients with idiopathic intracranial hypertension (IIH) and papilledema (PE) compared to healthy controls by applying non-invasive diffusion-weighted MRI. MethodsA retrospective analysis of diffusion-weighted MR images of 5 patients with IIH (10 ONs), mean age: 31 +/- 10 years (5 women), and 11 healthy controls (22 ONs, mean age: 60 +/- 13 years, 5 women) was performed. The flow velocity flow-range ratio (FRR) between the intracranial cavity and the SAS of the ON was calculated in both groups and then compared. ResultsThe mean FRR was 0.55 +/- 0.08 in patients with IIH and 0.63 +/- 0.05 in healthy controls. The difference between patients with IIH and healthy controls was statistically significant (p < 0.05). ConclusionsThe CSF flow velocity was decreased in patients with IIH with PE compared to healthy controls. The reduced CSF flow dynamics might be involved in the pathophysiology of PE in IIH and diffusion-weighted MRI can be a useful non-invasive tool to study the CSF flow dynamics within the SAS ON. Idiopathic intracranial hypertension is a neurological disease, where vision loss is the most feared complication of this disorder. The pathophysiology of IIH is not fully understood but is strongly linked to a reduced uptake of CSF into the central dural sinus veins. In this study, we examined the CSF flow rates in the SAS ON and the brain in patients with IIH and PE compared to healthy controls by applying non-invasive diffusion-weighted MRI. Knowing about the flow ratio of CSF may be of clinical relevance for the treatment decisions of IIH. If medical treatment fails, surgical options for lowering the ICP pressure need to be taken into consideration. As the primary goal of treatment is to prevent the loss of vision and visual field, it is important to know whether the communication of CSF between the intracranial CSF and the CSF in the perioptic space is intact. We showed that the CSF flow velocity was decreased in IIH patients with PE compared to healthy controls. The reduced CSF flow might be involved in the pathophysiology of PE in IIH, and diffusion-weighted MRI can be a useful non-invasive tool to study the CSF flow dynamics within the SAS ON.

Purpose: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., antievascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system.

Design: Review of evidence-based literature, along with expert consensus opinion. Participants: International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men.

Methods: The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification.

Main Outcome Measures: Consensus statement.

Results: The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae.

Conclusions: These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care.

Background: Open-angle glaucoma (OAG) and Alzheimer's disease (AD) are two age-related neurodegenerative diseases of significant public health importance. Epidemiological studies have indicated that there might be an association between the disorders.

Methods: Predictors of AD, including mixed and unspecified dementia, were analysed in a cohort of 712 residents aged 65-74 years, examined in a population survey in the rural district of Tierp, Sweden, from 1984 to 1986. To expand the sample size, 821 people were recruited by means of glaucoma case records established at the Eye Department in Tierp from 1978 to 2007. In this way, the cohort comprised 1,533 people, representing more than 21,000 person-years at risk. Medical records were reviewed to identify subjects diagnosed with dementia. Those with a follow-up duration shorter than 2 years were excluded.

Results: By the conclusion of the study, in August 2020, 307 subjects had received a diagnosis of AD, including mixed and unspecified dementia. Of these cases, 55 were affected with definite OAG at baseline. Higher age and ischemic heart disease were the only predictors of AD identified. In multivariate analysis, adjusting for age, participation in the population survey and competing events, no association was found between OAG and AD (hazard ratio 1.08; 95% confidence interval: 0.80-1.47).

Conclusion: In this long-term follow-up study of subjects aged 65-74 years old in Sweden, OAG was not associated with AD.

Purpose To assess the relationship of age-related cataract with all-cause mortality in a Swedish population. Methods Cox regression analyses were performed in a cohort of 746 residents 65-74 years of age, examined in a population survey in the rural district of Tierp, Sweden, 1984-86. To expand the sample size, 1,071 people were recruited by means of glaucoma case records established at the Eye Department in Tierp from 1978 to 2007. In this way, the cohort comprised 1,817 subjects, representing nearly 27,000 person-years at risk. The presence of cataract was determined based on retroillumination with lens opacities evident on slit-lamp examination. Information on deaths was obtained from the local population register. Results By the conclusion of the study in April 2020, 1,633 deaths had been reported. Of these cases, 694 were affected by lens opacities or had history of cataract surgery at baseline. In multivariate analysis, including cataract, age, sex, smoking habits, cancer, diabetes, hypertension and ischemic heart disease, no association was found between cataract and mortality (hazard ratio 0.99; 95% confidence interval 0.90-1.10). Adjustment for participation in the population survey had no effect on the estimate. Conclusion In this long-term follow-up study of subjects 65-74-years-old in Sweden, cataract was not associated with all-cause mortality.

Purpose: To estimate the incidence of pseudoexfoliation (PEX) and its associated risk factors in a defined population in Sweden.

Methods: The development of PEX was studied in a cohort of 489 residents aged 65-74 years, examined in a population survey in the municipality of Tierp 1984-1986. To expand the sample size, 576 people were recruited by means of glaucoma case records established at the Eye Department in Tierp in 1978-2007. In this way, the cohort comprised 1065 subjects, representing nearly 10 500 person-years at risk. Incidence rates with 95% confidence intervals (CIs) were calculated. Survival analyses were performed to identify predictors for PEX. Those with a follow-up time shorter than 1 year were excluded.

Results: By the end of the study in November 2018, 179 new cases of PEX had been found. Of these, 78 had participated in the population survey, equal to an incidence rate of 14.8 per 1000 person-years (95% CI 11.5-18.1). The development of PEX was associated with higher age (hazard ratio 1.08 per year; 95% CI 1.03-1.13) and female gender (hazard ratio 1.59; 95% CI 1.16-2.18).

Conclusion: In this study on a Swedish population, the incidence of PEX was high. Increasing age and female gender were the only predictors for PEX identified.

BACKGROUND: Visual tracking of moving objects requires sustained attention and prediction of the object’s trajectory. We tested the hypothesis that measures of eye-head tracking of moving objects are associated to long-term neurodevelopment in very preterm infants.METHODS: Visual tracking performance was assessed at 4 month’s corrected age in 57 infants with gestational age <32 weeks. An object moved in front of the infant with sinusoidal or triangular (i.e. abrupt) turns of the direction. Gaze gain, smooth pursuit gain, and timing of gaze to object motion were analyzed. At 6.5 years the Wechsler Intelligence Scale for Children (WISC-IV), the Brown Attention Deficit Disorder (Brown ADD), and visual examination were performed. 

RESULTS: Gaze gain and smooth pursuit gain at 4 months were strongly related to all WISC-IV parameters at 6.5 years. Gaze gain for the triangular and sinusoidal motion patterns related similarly to the cognitive scores. For the sinusoidal motion pattern, timing related to most Brown ADD parameters. There were no statistically significant differences in associations dependent on motion pattern. Visual function did not influence the results. 

CONCLUSION: The ability to attend to and smoothly track a moving object in infancy is an early marker of cognition and attention at 6.5 years. 

PAX6 gene mutations cause a variety of eye and central nervous system (CNS) abnormalities. Aniridia is often accompanied by CNS abnormalities such as pineal gland atrophy or hypoplasia, leading to disturbed circadian rhythm and sleep disorders. Less is known on the coincidence of narcolepsy in this patient group. We aimed to find out whether the circadian rhythm or sleep-wake structure was affected in patients with aniridia. Four members of a family segregating with congenital aniridia in two generations were included in the study. The patients were subjected to genetic testing for a PAX6 mutation, multiple sleep latency test, whole-brain magnetic resonance imaging (MRI), hypocretin-1 in cerebrospinal fluid, and Human Leukocyte Antigen DQ beta1*06:02. All four members were heterozygous for the pathogenic c.959-1G>A mutation in the PAX6 gene. Sleep disturbance was observed in all family members. The index patient was diagnosed with narcolepsy. MRI showed a hypoplastic pineal gland in all members. We describe the first case of a patient with PAX6 haploinsufficiency, aniridia and pineal gland hypoplasia diagnosed with narcolepsy type-1, suggesting a complex sleep disorder pathogenesis.

Importance Optic nerve (ON) dysfunction is a common feature of different diseases. The pathophysiology is not yet fully understood. Background This study describes five patients with ON sheath (ONS) compartment syndrome (ONSCS) and contributes to the hypothesis that impaired cerebrospinal fluid (CSF) flow can play a role in the development of ON dysfunction. Design Retrospective case series. Participants Five patients with ONSCS were included in the study. Methods Elaboration of medical histories and clinical and diagnostic findings over a long time period was carried out by analysing medical records and by a detailed medical consultation. Main Outcome Measures The main outcome measures include clinical history; visual acuity; field, intraocular and CSF pressures; and contrast-loaded computed tomographic (CT) cisternography. Results Compartmentation of the ONS demonstrated by contrast-loaded CT cisternography was the consistent finding in all five patients who demonstrated findings of ON dysfunction. The aetiologies varied and included meningitis, papilloedema, sphenoid wing meningioma, disc herniation and normal-tension glaucoma. Conclusion and Relevance Compartmentation of the ONS with consecutively impaired CSF dynamics within the ON subarachnoid space can lead to ON dysfunction. Different aetiologies can cause the development of ONSCS.

BACKGROUND/AIMS:

During the last decade, improved neonatal care has resulted in increased survival of the most immature infants and improved health of more mature infants. We hypothesise that this has affected incidence and treatment of retinopathy of prematurity (ROP), enabling guidelines for screening to be modified.

METHODS: 

In Sweden, all infants with gestational age (GA) at birth ≤30 weeks are screened for ROP. Results are registered in a web-based register, Swedish National ROP Register, with a coverage rate of 97%. Incidence of ROP and frequency of treatment, aspects on natural course of ROP and number of examinations, are calculated in relation to GA at birth in infants born during 2008-2017.

RESULTS: 

Of 7249 infants, 31.9% (2310) had ROP and 6.1% (440) were treated. No infant with GA 30 weeks was treated. Incidence of ROP remained similar, but frequency of treatment increased (p=0.023). Over time, GA and birth weight were reduced in infants with ROP and with treated ROP. In the most immature infants, postmenstrual age was lower and postnatal age was higher when any ROP and stage 3 ROP were first detected (p<0.001). At treatment, postmenstrual but not postnatal age of the infant was associated with GA (p<0.001). During the 10-year period, 46 038 examinations were performed.

CONCLUSION: 

Modification of Swedish guidelines is proposed, including only infants with a GA of <30 weeks and postponing the first examination with 1 week in infants with GA 26-29 weeks. This would spare many infants from stressful examinations and reduce eye examinations with at least 20%.

Background Cataract is a major cause of visual impairment worldwide. There is a paucity of prevalence studies from Sweden. Therefore, we report the prevalence of cataract and its risk factors in a population-based study of older adults in Sweden. Methods The Tierp Glaucoma Survey was conducted in the municipality of Tierp, Sweden, including 760 subjects aged 65-74 years. The presence of cataract was determined based on retroillumination, with lens opacities evident on slit-lamp examination. To assess risk factors for cataract, odds ratios (ORs) were calculated, adjusted for age and gender. Results A total of 234 individuals were found to have cataract, 12 of whom had undergone cataract surgery. The prevalence adjusted for nonparticipation was 31.5% (95% confidence interval [CI] 29.4-33.6), 35.2% (95% CI 28.7-41.8) in females and 26.2% (95% CI 19.8-32.6) in males. Cataract was associated with age >= 70 years (OR 1.93; 95% CI 1.41-2.64), female gender (OR 1.54; 95% CI 1.12-2.11), and myopia (OR 2.3; 95% CI 1.16-3.56), while pseudoexfoliation, smoking, diabetes, hypertension, and ischaemic heart disease were not. Conclusion Nearly one-third of the sample were estimated to have lens opacities, or had undergone cataract surgery, making cataract a frequent disorder of older age. The study provided further evidence that increasing age, female gender, and myopia are associated with cataract.

Aim

The aim of the study was to investigate cognitive outcomes at 6.5 years in children born very preterm, in relation to neonatal characteristics and 2.5-year neurodevelopment.

Methods

A prospective cohort, with gestational age 22.3-31.9 weeks, born 2004-2007, were examined at 2.5 years with the Bayley Scales of Infant and Toddler Development (Bayley-III) (n = 100) and at 6.5 years with the Wechsler Intelligence Scales (n = 91).

Results

Neonatal factors independently related to 6.5-year outcome were gestational age, retinopathy of prematurity and treated persistent ductus arteriosus. The Bayley-III cognitive scores explained only 44% of the Full-Scale Intelligence Quotient result at 6.5 years, and 22% of the children had Wechsler index results below −1 SD, indicating cognitive impairment, after average test results at 2.5 years. The relative risk to score below −1 SD on the Full-Scale IQ was 2.83 (95% CI 1.45-5.53) in children with gestational age below 28 weeks and 2.22 (95% CI 1.18-4.17) at gestational age 28-31 weeks.

Conclusion

Very preterm infants born in the 2000s had increased risks for impaired cognition at 6.5 years, but individual predictions based on neonatal risks and 2.5-year test results were not enough to identify all high-risk children.