Following prevalence of myopia in a large Swiss military cohort over the last decade: where is the European "myopia boom"?

PURPOSE: Myopia prevalence is increasing globally, with the highest rates found in Asia. Data from European countries is scarce. We aimed to investigate whether the prevalence of myopia is rising in our meridians. METHODS: Data from male military conscripts for the recruitment period of 2008-2017 were retrospectively analyzed. Year of recruitment, conscripts' birth year, visual acuity, refractive status (spherical equivalent), and spectacle wear (yes/no) were available. RESULTS: The dataset contained data of a total of 355,657 male conscripts, who had been recruited in the years 2008 to 2017. The mean number of conscripts per year was 35,566 (MD = 35,440, SD = 1249), reaching a minimum number of 33,998 conscripts in 2017 and a maximum of 37,594 in 2011. Mean age at recruitment was 19.7 years (MD = 19.0 years, SD = 1.1 years). Overall, the number of conscripts wearing spectacles remained stable over the observation time; on average 29.6% (n = 10,540; MD = 10,472; SD = 492) of conscripts wore glasses at recruitment. Of 21.8% (n = 77,698) of conscripts, data on the refractive status was available: The mean spherical equivalent for both right and left eyes was -2.3D (MD = -2 D, SD = 2.4 D). No decrease in mean spherical equivalent per recruitment year was noted over the observation period. Estimated myopia prevalence reached an average of 27.5% (SD = 0.8%) and did not increase during the observation period. CONCLUSION: In summary, no change in spherical equivalent refractive errors of male Swiss army conscripts was found for the years 2008-2017. Equally, the percentage of spectacle wearers (MN = 29.6%) and estimated myopia prevalence (MN = 27.5%) did not significantly increase during the observation time. TRIAL REGISTRATION:  BASEC 2019-00060 (18/01/2019).

Cyclotorsion Measurement on Scanning Laser Ophthalmoscopy Imaging Compared With Fundus Photography in Patients With Fourth Nerve Palsy and Healthy Controls: CySLO-IV Study.

BACKGROUND: The purpose of the study is to evaluate the agreement of the foveopapillary angle (FPA) on conventional fundus photography (c-FPA) with the FPA on scanning laser ophthalmoscopy (SLO) imaging (SLO-FPA) in patients with fourth nerve palsy and healthy controls (HCs). METHODS: The FPA was measured in both eyes of 25 patients and 25 HCs in synedra View (c-FPA) and with the integrated algorithm of the Heidelberg Spectralis OCT (SLO-FPA). The primary endpoint was the agreement of both measurements. Furthermore, we evaluated the influence of the eye tracker, the influence of fixation on objective torsion, and the FPA cutoff between patients and HCs. RESULTS: The mean SLO-FPA in patients (6/25 acquired palsies) was 11.3 ± 3.6° and 6.4 ± 2.1° in HCs. The mean c-FPA was 11.4 ± 4.0° and 5.8 ± 2.2°, respectively. The Bland-Altman plot of c-FPA vs SLO-FPA in patients and HCs shows no systematic bias (mean of -0.28°). Limits of agreement were -6.58 and 6.02°. Using the eye tracker had no systematic effect. There was no evidence for an immediate shift of torsion with change of fixation (24/25 patients and 23/25 HCs). Discrimination between patients and HCs by the SLO-FPA is very good with an area under the curve = 0.92 (95% confidence interval: 0.84-0.99). CONCLUSIONS: SLO-FPA measurement allows convenient and consistent assessment of objective cyclotorsion. There was no systematic bias in the difference between SLO-FPA and traditional c-FPA; thus, SLO-FPA is a valuable alternative to the commonly used c-FPA. Using the eye tracker is recommended for proper centering of the ring scan.

Reliability of Cyclotorsion measurements using Scanning Laser Ophthalmoscopy imaging in healthy subjects: the CySLO study.

BACKGROUND/AIMS: To evaluate inter-rater and intra-rater reliability of objective cyclotorsion measurements obtained in healthy subjects using the Heidelberg Spectralis spectral domain-optical coherence tomography (SD-OCT) device. METHODS: In this prospective methodological study, 32 healthy subjects (14 men, 18 women; aged 21-64 years) were enrolled, 31 right eyes were examined and their foveo-papillary angles (FPAs) were measured. The retinal nerve fibre layer (RNFL) programme by Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) was used to measure cyclotorsion based on the in-built algorithm for the measurement of the FPA on the scanning laser ophthalmoscopy (SLO) image. Repeated scans of the fixating and non-fixating right eye without and with eye tracker each were obtained by three different examiners. RESULTS: The mean FPA measured overall by all three examiners was 6.6°±2.8°. The inter-rater reliability of the measured FPAs using the linear mixed effects model is estimated as rhointer=0.8803. The intra-rater reliability is estimated as rhointra=0.9589. CONCLUSIONS: Repeatability of objective cyclotorsion measurements within and between observers using the Heidelberg Spectralis OCT is very high. SD-OCT/SLO imaging is a reliable imaging technique to measure and study cyclotorsion. CLINICAL TRIAL NUMBER: NCT02631369, Results.

Lipocalin-like prostaglandin D synthase (L-PGDS) concentration in aqueous humour in patients with open-angle glaucoma.

PURPOSE: To report on the concentration of lipocalin-like prostaglandin D synthase (L-PGDS) in the aqueous humour (AH) in patients with open-angle glaucoma (OAG). PATIENTS AND METHODS: Prospective assessment in 20 patients (13 female, 7 male, mean age 74±10.6 y) who underwent surgery for OAG. AH was sampled and analyzed for L-PGDS concentration. AH from 26 patients (11 female, 15 male, 72.4±14.4 y) without glaucoma who underwent cataract surgery, served as control subjects. RESULTS: The L-PGDS concentration in the AH sampled from the anterior chamber in the OAG group (5.9±2.4 mg/L) was significantly (P<0.001) higher than in the control group (3.3±1.3 mg/L). There were no significant differences between the concentrations of L-PGDS between the left and the right eye or between genders. CONCLUSIONS: L-PGDS concentration in the AH of patients with OAG was significantly elevated compared with its concentration in the AH of nonglaucomatous eyes. As L-PGDS is a biologically pluripotent protein, its possible role in glaucoma warrants further examination.

Changes in the amygdala produced by viewing strabismic eyes.

PURPOSE: The aim of this study was to look for the response to strabismus images in the limbic network (amygdala, hippocampus, parahippocampus) of healthy volunteers and to compare it with their reaction to viewing normal eyes. DESIGN: Prospective, observational study. PARTICIPANTS: Thirty-one healthy volunteers underwent functional magnetic resonance imaging (fMRI). METHODS: Functional magnetic resonance imaging data and blood oxygen level-dependent signal changes were analyzed using the BrainVoyager QX software package (Brain Innovation, Maastricht, The Netherlands). MAIN OUTCOME MEASURES: Responses to viewing strabismus images were compared with those observed while viewing normal eye images. RESULTS: Strabismus images led to significant activation of the amygdala, hippocampus, parahippocampal, and fusiform gyri in 30 of 31 subjects compared with normal eye images, indicating a negative emotional response. CONCLUSIONS: These fMRI results confirm that strabismus influences organically not only the patient with nonparallel eyes but also observers. Treatment of strabismus therefore changes the interpersonal dynamic for patients with strabismus on a demonstrable organic basis. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prediction of the clinical outcome of cavernous sinus lesions in children.

To identify predictive findings in children with nontraumatic acquired cavernous sinus lesions, a retrospective study of the clinical course of 4 of our own patients and 17 more children found in an extensive literature search was performed. Mean age was 8.7 years. Malignancy was found in 11 of 21 children (6 female, 15 male). Of these 21 children, 9 were cured, 8 are either in remission or their course is unknown, and 4 died. Eight of the nine cured patients were diagnosed as having had Tolosa-Hunt syndrome. Of the four deceased children, three had a very short course (1 to 4 months) and were diagnosed with malignant lymphoma (n = 2) and rhabdomyosarcoma (n = 1). One patient died from a brain tumor other than the initially diagnosed T-cell lymphoma in the cavernous sinus after a follow-up of 8 years. MRI should be the preferred imaging technique-even if it is not conclusive in many cases-and every possible diagnostic effort should be made before using corticosteroids. No clinical or radiological signs other than rapid deterioration seem to be predictable of a malignant cavernous sinus lesion with poor outcome. Thus, close follow-up is recommended in children with signs and symptoms indicative of an acquired lesion in the cavernous sinus.

Cerebrospinal fluid exchange in the optic nerve in normal-tension glaucoma.

AIM: To report on the cerebrospinal fluid (CSF) exchange between the intracranial spaces (ie, basal cisterns) and the subarachnoid space (SAS) of the optic nerve (ON) in subjects with normal-tension glaucoma (NTG) compared with control subjects without NTG or other forms of glaucoma. METHODS: CT cisternography of the brain and orbits was performed in 18 patients with NTG (7 women, 11 men; mean age 64.9 ± 8.9 years) and in four patients without glaucoma or intracranial disease (4 women; mean age 62.8 ± 18.4 years). The density of contrast-loaded cerebrospinal fluid (CLCSF) in the intracranial spaces and in the SAS surrounding the ONs was measured in Hounsfield units. STUDY DESIGN: Unmasked, prospective series. Statistical analysis was performed using an independent two-tailed t test and the non-parametric Spearman correlation test. RESULTS: The density of CLCSF in the SAS surrounding the ONs in the NTG group was significantly reduced compared with its density in the intracranial CSF spaces and in the SAS of ONs measured in the control group (p=0.006). There were no significant differences between men and women within the NTG group (p>0.35). CONCLUSIONS: The finding of a difference in the concentration gradients between the CLCSF within the intracranial spaces and the SAS of the ONs in this group of NTG patients compared with control subjects supports the hypothesis of a disturbed CSF exchange between the CSF in the intracranial spaces and the CSF in the SAS surrounding the ONs. The disturbance of CSF dynamics in this specific CSF pathway can be explained by ON compartmentation. The clinical importance of this finding warrants further investigation.

Meningothelial cells react to elevated pressure and oxidative stress.

BACKGROUND: Meningothelial cells (MECs) are the cellular components of the meninges enveloping the brain. Although MECs are not fully understood, several functions of these cells have been described. The presence of desmosomes and tight junctions between MECs hints towards a barrier function protecting the brain. In addition, MECs perform endocytosis and, by the secretion of cytokines, are involved in immunological processes in the brain. However, little is known about the influence of pathological conditions on MEC function; e.g., during diseases associated with elevated intracranial pressure, hypoxia or increased oxidative stress. METHODS: We studied the effect of elevated pressure, hypoxia, and oxidative stress on immortalized human as well as primary porcine MECs. We used MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) bioreduction assays to assess the proliferation of MECs in response to treatment and compared to untreated control cells. To assess endocytotic activity, the uptake of fluorescently labeled latex beads was analyzed by fluorescence microscopy. RESULTS: We found that exposure of MECs to elevated pressure caused significant cellular proliferation and a dramatic decrease in endocytotic activity. In addition, mild oxidative stress severely inhibited endocytosis. CONCLUSION: Elevated pressure and oxidative stress impact MEC physiology and might therefore influence the microenvironment of the subarachnoid space and thus the cerebrospinal fluid within this compartment with potential negative impact on neuronal function.

Cerebrospinal fluid segregation optic neuropathy: an experimental model and a hypothesis.

AIM: To describe the histological changes in the optic nerve (ON) after experimental segregation of cerebrospinal fluid (CSF). METHODS: In seven sheep, a silicone band was placed around one ON to compress the subarachnoid space (SAS) surrounding the nerve, thus blocking the flow of CSF without compressing the ON itself. After 4 or 21 days, both the ligated and untouched ONs were removed and evaluated histologically. RESULTS: All treated ONs showed marked loss of axons, destruction of myelin and swelling of meningoepithelial cells, most pronounced in the proximal ON adjacent to the globe at the location most distant to the ligature. There was no significant difference in histological findings between the ONs that were ligated for 4 days and those with 21 days of ligature. CONCLUSION: CSF segregation in the ON by blocking the SAS leads within 4 days to severe nerve damage. The increasing severity of these changes with increasing distance from the site of the ligature argues against simple pressure- or microperfusion-dependent effects and supports the hypothesis that interruption of CSF flow in the SAS of the ON can produce damage due to a change of CSF flow and content.

The daily walking distance of young doctors and their body mass index.

CONTEXT: Non-exercise physical activity thermogenesis (NEAT) has been shown to differ in obese and non-obese subjects. OBJECTIVE: To explore whether NEAT is determined by the body mass index (BMI) even within the normal range, we hypothesized that the daily walking distance of young doctors in training at a teaching hospital is inversely correlated with the BMI. DESIGN: Prospective, single blind, controlled trial. SETTING: Identical wards of a 400 bed university-based teaching hospital, highly standardized for patient number treated, the severity of disease, the clinical experience of the doctors and their time spent in the institution. INTERVENTION: The walking distance was measured daily by a pedometer over one week and standardized for the setting, workload, and insurance status. MAIN OUTCOME MEASURES: Mean daily walking distance as a measure of NEAT. RESULTS: The mean daily distance walked was 2323+/-627 m with a more than 4-fold difference between the daily maximum of 4310 m and the minimum of 1003 m. There was an inverse correlation of the walking distance with the BMI (Spearman rho=0.750, p=0.02), and with the time spent in the hospital (rho=-0.800, p=0.01), but not with the months of clinical experience, age, gender, number of patients, disease, severity nor with the insurance status of the patients cared for. There was no mean difference between the distance walked in the morning vs. in the afternoon nor was there a trend from Monday through Friday. CONCLUSION: The results of this pilot study indicate that NEAT is related to the BMI in the non-obese stage.

Papilledema revisited: is its pathophysiology really understood?

The term 'papilledema' is used to describe swelling of the optic disc that is thought or known to be associated with increased intracranial pressure (ICP) transmitted to the subarachnoid space (SAS) surrounding the optic nerve (ON). In most cases, the diagnosis of increased ICP is confirmed by lumbar puncture, the results of which are believed to represent the pressure in all of the cerebrospinal fluid (CSF) spaces. Until recently, all CSF spaces were thought to communicate freely and that CSF pressure and composition in one location were the same throughout the central nervous system (CNS) unless there was an acquired structural disturbance. However, the concept of continuous CSF flow and pressure throughout the CNS does not explain why some patients with elevated ICP do not develop papilledema, why some patients have highly asymmetrical papilledema, or why some patients with papilledema have normal ICP during 24-hour monitoring. In addition, CSF sampling during lumbar puncture and during ON sheath fenestration demonstrates an increased concentration of lipocalin-like prostaglandin D synthase, a substance toxic to astrocytes, in the SAS of the ON compared with that in the lumbar CSF space, and also a difference in CSF dynamics between the lumbar and ON SAS in some patients with papilledema. We therefore suggest that papilledema does not result from raised ICP alone but in some cases by compartmentation of the SAS of the ON, leading to a toxic milieu around the nerve.

'Spontaneous' periocular hemorrhage and macrohematuria.

PURPOSE: To report on a 19-year-old man with 'spontaneous' periocular hemorrhage and macrohematuria as the first signs of a bone-marrow-infiltrating rhabdomyosarcoma of the left superior rectus muscle. PROCEDURES: Clinical eye examination, magnetic resonance imaging, laboratory workup and bone marrow biopsy were performed. RESULTS: Magnetic resonance imaging showed a mass lesion in the left superior rectus muscle. While funduscopy had initially been normal, optic disc swelling, retinal hemorrhage and vitreous cell infiltration could be seen in the further course of disease. Laboratory work-up showed macrohematuria, thrombocytopenia and decreased concentration levels of plasma fibrinogen. Thromboplastin time was decreased. A bone marrow biopsy revealed small cell infiltration; using immunohistochemistry, a rhabdomyosarcoma was diagnosed. Unfortunately, the patient died few months later, in spite of chemotherapy. CONCLUSION: 'Spontaneous' periocular hemorrhage and macrohematuria were the first signs of a bone-marrow-infiltrating rhabdomyosarcoma in this young and otherwise healthy patient.

Does immunohistochemistry allow easy detection of lymphatics in the optic nerve sheath?

We evaluated the validity of anti-D2-40 and anti-LYVE-1 (antibodies against lymphatic endothelium) for IHC diagnosis and semiquantification of lymphatic vessels in the dura mater of the intraorbital portion of the human optic nerve (ON). Fourteen specimens were analyzed using light microscopy within 12 hr postmortem. We found in all specimens that both D2-40 and LYVE-1 stained lymphatic vessels as well as venules and arterioles. Our findings show lymphatic vessels in the meninges of the intraorbital portion of the human ON. Anti-D2-40 and anti-LYVE-1 antibodies, however, are not found to be exclusively specific to the endothelial layer of lymphatics because they also stain the endothelial layer of venules and arterioles. For the unequivocal identification of lymphatics, additional morphological criteria are necessary. Nevertheless, D2-40 and LYVE-1 staining allows rapid identification of endothelial layers.

Is open-angle glaucoma caused by impaired cerebrospinal fluid circulation: around the optic nerve?

Chronic open-angle glaucoma is the most frequent type of glaucoma and a leading cause for blindness. The role of intraocular pressure (IOP) in the pathogenesis of open-angle glaucoma has been challenged by patients with typical glaucomatous optic disc changes and visual field loss in whom the IOP never exceeded normal values (normal-tension glaucoma), as well as by patients with persistently elevated IOP who do not develop glaucomatous disc or field changes. Recent research has demonstrated that the cerebrospinal fluid (CSF) is not evenly distributed in all CSF spaces and that the subarachnoid space of the optic nerve can turn into a CSF compartment on its own. The biochemical components in this optic nerve compartment can differ markedly from normal CSF and some of its components (such as L-PGDS) may produce a toxic effect on the optic nerve and may therefore play an important role in the pathophysiology of open-angle glaucoma.

Lipocalin-like prostaglandin D synthase in subretinal fluid of detached retinas in humans.

BACKGROUND: The presence of lipocalin-like prostaglandin D synthase (L-PGDS), a dominantly brain derived protein in the cerebrospinal fluid (CSF) with a low concentration in serum, in the subretinal fluid (SRF) of detached retinas, has not been reported. L-PGDS has been demonstrated in the ciliary body and the retinal pigment epithelium in rats. METHODS: SRF was sampled during surgery (scleral buckling) of rhegmatogenous retinal detachments in 20 eyes. Biochemical and nephelometric analysis for L-PGDS concentration were performed. Albumin concentrations were determined in the same samples. RESULTS: L-PGDS concentrations in SRF (mean 18.9 mg/L +/- 14.8 mg/L) were markedly higher than the normal L-PGDS concentration in serum (<0.55 mg/L) and appears to decrease with the duration of the retinal detachment (P = 0.0064). CONCLUSIONS: As the subretinal space is not accessible in attached retinas there are no data on normal levels of L-PGDS in the subretinal space. The L-PGDS concentrations measured in the SRF of detached retinas are on average 34 times higher than normal L-PGDS serum concentration and about in the range of normal L-PGDS CSF concentration (15.3 mg/L). As the concentrations of L-PGDS exceed normal serum levels, a choriocapillary transudation is highly improbable as the source of L-PGDS in SRF of detached retinas.

Complete recovery of visual acuity in two patients with giant cell arteritis.

Visual recovery in GCA patients is rare even when treated with HDMP. Treatment is therefore believed to be effective mainly in saving the unaffected eye. We report on two cases with biopsy-proven GCA in which complete recovery of VA occurred under intravenous HDMP.

Is silicone oil optic neuropathy caused by high intraocular pressure alone? A semi-biological model.

BACKGROUND: Silicone oil endotamponade is used for the repair of complicated retinal detachments. Cataract, glaucoma and corneal endothelial dysfunction are the most frequent complications of silicone oil tamponade. Clinical and histopathological studies have revealed that silicone oil can penetrate into the optic nerve and into the brain. The mechanism by which silicone oil moves from intraocular into the optic nerve is still under debate. To investigate the effect of intraocular pressure only, a post-mortem experimental histological study was performed to determine whether silicone oil penetration from the globe into the optic nerve after vitrectomy and silicone oil instillation is a purely pressure-related phenomenon. Although a post-mortem study excludes physiological processes, it serves as a model for the study of pure physical forces onto biological structures. METHODS: The study was carried out on 20 human eyes with their optic nerves attached. All specimens had been harvested from patients without known eye disease. The vitreous body was removed with a syringe and the globe was filled with silicone oil. A lipophil fluorescence marker (Bodipy) was added in 8 eyes. The mean intraocular pressure after silicone oil filling measured 40 mm Hg and the globes stayed under pressure for up to 16 weeks. The eyes and optic nerves were stained with H&E and examined with light, phase-contrast and fluorescence microscopy. RESULTS: None of the 20 specimens examined showed silicone oil in the retrolaminar portion of the optic nerve. CONCLUSIONS: Migration of silicone oil into the optic nerve was not demonstrated in this human post-mortem study. Therefore other factors, such as pre-existing glaucomatous damage to the disc region and/or active transport mechanisms must be involved in the development of silicone oil-associated optic neuropathy.