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Background/objectives: We aimed to measure cerebrospinal fluid (CSF) flow rates in the subarachnoid space (SAS) of the optic nerve (ON) by applying non-invasive diffusion-weighted MRI in patients with normal tension glaucoma (NTG) compared to age-matched controls.

Subjects/methods: In this prospective study, an analysis of diffusion-weighted images of 26 patients with NTG (49ONs) and age-matched volunteers (52ONs) was conducted. Subjects were classified into 4 groups: group I (50-59 y., n = 12 eyes), group II (60-69 y., n = 16 eyes), group III (70-79 y., n = 18 eyes) and group IV ( > 80 y., n = 6 eyes) for NTGs and healthy volunteers, respectively. The flow-range ratio (FRR) between the frontal lobe SAS and the SAS of the ON was calculated for each age category group and then compared between age-categories as well as between NTGs and controls.

Results: The mean FRR for age groups were (I) 0.54 +/- 0.06 and 0.62 +/- 0.03 (p < 0.05), (II) 0.56 +/- 0.08 and 0.63 +/- 0.03 (p < 0.05), (III) 0.54 +/- 0.06 and 0.62 +/- 0.02 (p < 0.001) as well as (IV) 0.61 +/- 0.03 and 0.61 +/- 0.04, for NTGs and controls, respectively. Using pooled data, the difference between the FRR in NTGs and controls was statistically significant (p < 0.0001). There were no statistically significant differences within the age categories of the control group. When comparing the FRR of NTGs by age categories, no statistically significant difference was found between the subgroups.

Conclusions: FRR was significantly reduced in NTGs compared to age-matched controls without any significant differences within the age groups themselves. Given the physiological importance of CSF for the integrity of neurons, axons and glial cells, reduced CSF flow dynamics might be part of the underlying neurodegenerative process of NTG.

OBJECTIVES: To determine if current clinical use of iodine contrast media (ICM) for computerised tomography (CT) increases the risk of acute kidney injury (AKI) and long-term decline in renal function in patients treated in intensive care.

METHODS: A retrospective bi-centre cohort study was performed with critically ill subjects undergoing either ICM-enhanced or unenhanced CT. AKI was defined and staged based on the Kidney Disease Improve Global Outcome AKI criteria, using both creatinine and urine output criteria. Follow-up plasma creatinine was recorded three to six months after CT to assess any long-term effects of ICM on renal function.

RESULTS: In total, 611 patients were included in the final analysis, median age was 65.0 years (48.0-73.0, quartile 1-quartile 3 (IQR)) and 62.5% were male. Renal replacement therapy was used post-CT in 12.9% and 180-day mortality was 31.2%. Plasma creatinine level on day of CT was 100.0 µmol/L (66.0-166.5, IQR) for non-ICM group and 77.0 µmol/L (59.0-109.0, IQR) for the ICM group. The adjusted odds ratio for developing AKI if the patient received ICM was 1.03 (95% confidence interval 0.64-1.66, p = 0.90). No significant association between ICM and increase in plasma creatinine at long-term follow-up was found, with an adjusted effect size of 2.92 (95% confidence interval - 6.52-12.36, p = 0.543).

CONCLUSIONS: The results of this study do not indicate an increased risk of AKI or long-term decline in renal function when ICM is used for enhanced CT in patients treated at intensive care units.

CLINICAL RELEVANCE STATEMENT: Patients treated in intensive care units had no increased risk of acute kidney injury or persistent decline in renal function after contrast-enhanced CT. This information underlines the need for a proper risk-reward assessment before denying patients a contrast-enhanced CT.

KEY POINTS: • Iodine contrast media is considered a risk factor for the development of acute kidney injury. • Patients receiving iodine contrast media did not have an increased incidence of acute kidney injury or persistent decline in renal function. • A more clearly defined risk of iodine contrast media helps guide clinical decisions whether to perform contrast-enhanced CTs or not.

Visual hallucinations after central or peripheral impairment, commonly called Charles Bonnet syndrome, are often highly distressing and with few available treatment options. Here we report a case where an adolescent developed severely distressing visual hallucinations after hypoxic damage to the occipital cortex following a suicide attempt. The patient received active and sham occipital continuous theta-burst stimulation (cTBS) in a single-case experimental research design and a subsequent open phase, to evaluate cTBS as a Charles Bonnet treatment. The visual hallucinations seemed to decrease more during active than sham cTBS in the blind phase, and in the following week of repeated five daily treatments they almost disappeared. A normalization of increased activity in the lateral visual network after cTBS was observed on a functional magnetic resonance imaging resting-state analysis compared with 42 healthy controls. Visual evoked potentials stayed largely unchanged both in the sham-controlled blind phase and the subsequent open phase. During the two weeks after the open phase with repeated cTBS sessions, the visual hallucinations gradually reappeared and almost returned to the baseline level. Our findings suggest that active cTBS over the primary visual cortex can reduce visual hallucinations through modulation of downstream visual regions, though the effect is temporally limited.

BACKGROUND: Open-angle glaucoma (OAG) is a leading cause of irreversible blindness. There are no prospective studies on the risk of developing blindness in both eyes in individuals with definite OAG.

METHODS: A total of 354 patients with newly diagnosed OAG, who had participated in four studies conducted at the Eye Department in Tierp, Sweden, from 1979 to 2006, were included in the investigation. Using the World Health Organization's criteria for blindness, medical records, glaucoma case records, and visual fields were reviewed to identify patients who developed bilateral blindness. Incidence proportions and incidence rates were estimated. To assess potential risk factors for blindness, standardised morbidity ratios (SMRs) were calculated. The effects of age and sex were also analysed using Cox proportional hazard models.

RESULTS: By the end of the study in August 2023, 33 cases of blindness caused by OAG had been found, corresponding to an incidence proportion of 9.3% (95% confidence interval [CI]: 6.5-12.8%). Within the first 20 years, 29 cases were detected, yielding a proportion of 8.2% (95% CI: 5.5-11.6%). The incidence rate was estimated to be 8.6 per 1,000 person-years (95% CI: 5.9-12.6 per 1,000 person-years). Glaucoma-related blindness was associated with male sex (SMR 2.33; 95% CI: 1.13-4.80). The hazard ratio was doubled for every 5 year of increasing age (2.21; 95% CI: 1.60-3.05).

CONCLUSION: In this study of blindness in newly diagnosed OAG in a Swedish population, approximately one in 10 patients progressed to bilateral blindness caused by the disease. Old age and male sex were identified as significant risk factors.

Purpose To study predictors of open-angle glaucoma (OAG) in newly diagnosed patients detected in clinical practice in a defined population and to estimate the frequency of normal-tension glaucoma (NTG).

Methods Predictors of OAG were analysed in a case-control study, nested in a cohort of 481 people, 55-84 years of age, in two rural districts in Sweden, examined at the Eye Department in Tierp from 1988 to 2003. To make the sample complete, 63 residents first examined at the Uppsala University Hospital (UUH), 60 of whom were identified with the help of registers, were invited to attend the study. In this way, the cohort included 544 individuals. Automated perimetry was used to find cases of OAG.

Results In people first examined in Tierp, incident OAG was found in 99 subjects. Of these cases, six were diagnosed with NTG. Increased intraocular pressure (IOP), higher age, male sex, a positive family history, pseudoexfoliation (PEX), and haemorrhages of the optic disc were associated with OAG. In a logistic regression model including PEX, every increase in IOP by 5 mmHg increased the risk for OAG four-fold (odds ratio 4.04; 95% confidence interval 2.91-5.62). The effect of PEX was essentially mediated by increased pressure. The inclusion of the 63 subjects first examined at the UUH had no impact on the results.

Conclusion In this study on patients aged 55-84-years old in clinical practice in Sweden, increased IOP was strongly associated with incident OAG, while NTG was a rare finding.

Purposes: The aim of this study is to investigate the time evolution of active caspase 3 within first 120 h in the rat lens after in vivo exposure to subthreshold dose of UVR-B.

Methods: Twenty three six-week-old female albino Sprague-Dawley rats were exposed to subthreshold dose (1 kJ/m2) of UVR-B unilaterally and sacrificed at 24, 41, 70 and 120 h after exposure. Lenses were enucleated and active caspase 3 was detected by Western Blot. The time evolution of active caspase 3 was then plotted as a function of relative mean difference in active caspase 3 between exposed and nonexposed lenses.

Results: There is expression of active caspase 3 in both exposed and nonexposed lenses but there is no difference in relative mean difference in active caspase 3 between exposed and nonexposed lenses in all four postexposure groups.

Conclusions: Exposure to subthreshold dose of UVR-B does not induce apoptosis in the rat lens in vivo within first 120 h though there is a non-significant increase of active caspase 3 at 120 h. Increase in sample size might reduce the variation level in expression of active caspase 3 in the rat lenses.

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.

Background: Increased intraocular pressure (IOP) and pseudoexfoliation (PEX) are major risk factors for open-angle glaucoma (OAG), an age-related neurodegenerative disease of significant importance for public health. There are few studies on the distribution of IOP in populations where PEX is a common finding.

Methods: The distribution of IOP was studied in 733 subjects 65-74 years of age, examined in a population survey in the rural district of Tierp, Sweden, 1984-86. The difference between the right and left eye and the effect of which eye was measured first were examined. Odds ratios, adjusted for age and sex, according to Mantel-Haenszel (ORMH), were calculated to estimate predictors of increased IOP, defined as a pressure >= 20 mm Hg in either eye. The pressure was measured with Goldmann applanation tonometry. Automated perimetry was used to identify OAG.

Results: The distribution of IOP was close to that of other European- derived populations. The pressure in the first measured eye was higher than in the second measured eye. Increased IOP was related to OAG and PEX, ORMH 8.97 (95% confidence interval [CI] 3.84-20.9) and 2.40 (95% CI 1.53-3.76), respectively. An IOP >= 20 mm Hg increased the risk of having been diagnosed with diabetes (ORMH 1.83; 95% CI 1.08-3.09).

Conclusion: In this study of subjects 65-74-years- old in Sweden, the distribution of IOP was close to that of other European-derived populations. Although the difference was small, the pressure in the first measured eye was higher than in the second eye. Increased IOP was strongly related to untreated OAG and PEX.

Aim

Perceptual mechanisms in social functioning might promote interventions. We investigated relations between visual perception and social functioning, in preterm children.

Methods

A prospective preterm cohort born in Uppsala County, Sweden, in 2004–2007 and 49 full-term controls were examined at 12 years. Aspects of visual perception, including static shapes, emotions and time to detect biological motion, were related to social functioning and visual acuity.

Results

The preterm group comprised 25 extremely preterm children, EPT, born below 28 gestational weeks and 53 children born between 28 and 31 weeks. Preterm children had difficulties in perception of static shapes (p = 0.004) and biological motion (p < 0.001), but not in emotion perception, compared to controls. In the EPT children, poorer shape perception and lower scores on emotion perception were associated with more social problems (p = 0.008) and lower visual acuity (p = 0.004). Shape perception explained more variance in social functioning than emotion perception. In controls, fewer social problems were linked to faster biological motion perception (p = 0.04).

Conclusion

Static shape and biological motion perception was affected in the preterm groups. Biological motion perception was relevant for social functioning in full-term children. In EPT children, only shape perception was linked to social functioning, suggesting differential visual perception mechanisms for social deficits.

Purpose

Very preterm birth increases risk for neonatal white matter injury, but there is limited data on to what extent this persists into adolescence and how this relates to ophthalmological outcomes. The aim of this study was to assess brain MRI findings in 12-year-old children born very preterm compared to controls and their association with concurrent ophthalmological outcomes.

Methods

We included 47 children born very preterm and 22 full-term controls (gestational age <32 and >37 weeks, respectively). Brain MRI findings were studied in association with concurrent ophthalmological outcomes at 12-year follow-up.

Results

Evans index (0.27 vs 0.25, p<0.001) and a proposed “posterior ventricle index” (0.47 vs 0.45, p=0.018) were increased in children born very preterm. Higher gestational age associated with larger corpus callosum area (β=10.7, 95%CI 0.59–20.8). Focal white matter lesions were observed in 15 (32%) of very preterm children and in 1 (5%) of full-term controls. Increased posterior ventricle index increased risk for visual acuity ≤1.0 (OR=1.07×10¹¹, 95%CI=7.78–1.48×10²¹) and contrast sensitivity <0.5 (OR=2.6×10²⁷, 95%CI=1.9×10⁸–3.5×10⁴⁶). Decreased peritrigonal white matter thickness associated with impaired visual acuity (β=0.04, 95%CI 0.002–0.07).

Conclusion

More white matter lesions and evidence of lower white matter volume were found in children born very preterm compared with full-term controls at 12-year follow-up. The association between larger posterior ventricle index and reduced visual acuity and contrast sensitivity suggests disturbances of the posterior visual pathway due to diffuse white matter lesions.

Glaucoma is a chronic progressive disease that causes loss of retinal ganglion cells, which impairs the visual field. In optic coherence tomography (OCT) image, the retinal ganglion cell (RGC) axons in the optic nerve head (ONH) can be quantified as the minimal thickness from the ONH Pigmental epithelium Central Limit (OPCL) to the Inner limit of the Retina Closest Point (IRCP). Alternatively, the minimal cross-sectional surface area can be measured. In peripapillary atrophy, the morphometry of the retinal pigmental epithelium is affected.

Purpose: To design and test a new computational algorithm for estimation of Pigment epithelium to Inner limit of the Retina Minimal Area (PIMA) and evaluate a new method to estimate the Pigment epithelium to Inner limit of the Retina Minimal Distance (PIMD). OPCL can be detected and annotated by a deep learning algorithm in individuals with peripapillary atrophy.

Methods: A deep learning algorithm has been trained to automatically detect OPCL, IRCP and calculate PIMD. A new computational algorithm was developed to estimate PIMA in OCT images of young adults. The mean between the first and second version of estimating PIMD was evaluated. The difference of distance between the ONH center-OPCL and ONH center-atrophic edge was estimated in eyes with peripapillary atrophy.

Results: A 95% confidence interval for PIMA-2π was estimated to 1.97 ± 0.19 mm2 (df = 15). A confidence interval for the difference between PIMDv1-2π and PIMDv2-2π was 0 ± 1 μm (df = 15). A 95 % confidence interval for the mean difference between ONH-OPCL and ONH-atrophic edge was estimated to 692 ± 192 µm (df = 5).

Conclusions: The computational algorithm for estimation of PIMA was developed and applied. An initial analysis indicated the capacity of the deep learning algorithm to detect OPCL in subjects with PPA.

Keywords: deep learning, optic nerve head, ONH, retinal pigmental epithelium, RPE, PIMD, PIMD-2π, minimal distance, PIMA, PIMA-2π, minimal area, peripapillary atrophy, PPA, optic coherence tomography, OCT, glaucoma, quantification, retinal ganglion cell axons