The prevalence of internuclear ophthalmoparesis in a population-based cohort of individuals with multiple sclerosis.

BACKGROUND: Internuclear ophthalmoparesis (INO) occurs in 15-52% of individuals with multiple sclerosis (MS) and is reliably detected by infrared oculography. Methods for diagnosing INO with infrared oculography and the association between INO and MS characteristics need confirmation. We aimed to describe INO prevalence and the clinical characteristics of individuals with MS and INO in a population-based cohort of individuals with MS born in the year 1966 (Project Y). METHODS: Previously described thresholds for the versional dysconjugacy index (VDI), assessed with standardized infrared oculography, were used to detect INO in participants of project Y. Clinical characteristics, visual functioning and complaints were compared between individuals with MS with INO and individuals with MS without INO. RESULTS: Two-hundred-twenty individuals with MS and 110 healthy controls were included. VDI values exceeding the threshold for INO presented in 53 (24%) individuals with MS and 19 controls (13%). INO was associated with male sex, greater disability, worse cognition and worse arm function in individuals with MS. There was no association with disease duration, visual functioning or complaints. CONCLUSIONS: INO is prevalent among individuals with MS aged fifty-three and related to clinical characteristics of MS. INO was more frequently detected in healthy controls than previous studies, implying that oculography based diagnosis of INO requires further refinement.

Impaired saccadic eye movements in multiple sclerosis are related to altered functional connectivity of the oculomotor brain network.

BACKGROUND: Impaired eye movements in multiple sclerosis (MS) are common and could represent a non-invasive and accurate measure of (dys)functioning of interconnected areas within the complex brain network. The aim of this study was to test whether altered saccadic eye movements are related to changes in functional connectivity (FC) in patients with MS. METHODS: Cross-sectional eye movement (pro-saccades and anti-saccades) and magnetoencephalography (MEG) data from the Amsterdam MS cohort were included from 176 MS patients and 33 healthy controls. FC was calculated between all regions of the Brainnetome atlas in six conventional frequency bands. Cognitive function and disability were evaluated by previously validated measures. The relationships between saccadic parameters and both FC and clinical scores in MS patients were analysed using multivariate linear regression models. RESULTS: In MS pro- and anti-saccades were abnormal compared to healthy controls A relationship of saccadic eye movements was found with FC of the oculomotor network, which was stronger for regional than global FC. In general, abnormal eye movements were related to higher delta and theta FC but lower beta FC. Strongest associations were found for pro-saccadic latency and FC of the precuneus (beta band ß = -0.23, p = .006), peak velocity and FC of the parietal eye field (theta band ß = -0.25, p = .005) and gain and FC of the inferior frontal eye field (theta band ß = -0.25, p = .003). Pro-saccadic latency was also strongly associated with disability scores and cognitive dysfunction. CONCLUSIONS: Impaired saccadic eye movements were related to functional connectivity of the oculomotor network and clinical performance in MS. This study also showed that, in addition to global network connectivity, studying regional changes in MEG studies could yield stronger correlations.

Saccadic delay in multiple sclerosis: A quantitative description.

In multiple sclerosis (MS), eye movement disorders are common and can be quantified with infrared video-oculography. A well-known abnormality is internuclear ophthalmoplegia (INO). This study aims to describe saccadic abnormalities beyond INO and investigate their clinical relevance. A validated standardized infrared oculography protocol, DEMoNS, was used for quantifying saccadic eye movements in three different tasks in MS patients and healthy controls. The relationship between the saccadic parameters and disease characteristics was investigated. Furthermore, the association between saccadic parameters and visual functioning was analysed using logistic regression models, adjusted for possible confounders. This cross-sectional study included 218 subjects with MS and 58 healthy controls. The latency of all saccades was longer in MS patients than in healthy controls. This saccadic delay was larger in subjects with a longer disease duration and more disabled subjects. Furthermore, it was significantly related to presence of a lower vision-related quality of life. This study provided a comprehensive overview of performance of MS patients in different saccadic tasks, compared to healthy controls. Saccadic delay in MS patients was present in all saccadic tasks and was related to advancing disease and visual functioning in daily life.

Diagnosing and quantifying a common deficit in multiple sclerosis: Internuclear ophthalmoplegia.

OBJECTIVE: We present an objective and quantitative approach for diagnosing internuclear ophthalmoplegia (INO) in multiple sclerosis (MS). METHODS: A validated standardized infrared oculography protocol (DEMoNS [Demonstrate Eye Movement Networks with Saccades]) was used for quantifying prosaccades in patients with MS and healthy controls (HCs). The versional dysconjugacy index (VDI) was calculated, which describes the ratio between the abducting and adducting eye. The VDI was determined for peak velocity, peak acceleration, peak velocity divided by amplitude, and area under the curve (AUC) of the saccadic trajectory. We calculated the diagnostic accuracy for the several VDI parameters by a receiver operating characteristic analysis comparing HCs and patients with MS. The National Eye Institute Visual Function Questionnaire-25 was used to investigate vision-related quality of life of MS patients with INO. RESULTS: Two hundred ten patients with MS and 58 HCs were included. The highest diagnostic accuracy was achieved by the VDI AUC of 15° horizontal prosaccades. Based on a combined VDI AUC and peak velocity divided by amplitude detection, the prevalence of an INO in MS calculated to 34%. In the INO group, 35.2% of the patients with MS reported any complaints of double vision, compared to 18.4% in the non-INO group (p = 0.010). MS patients with an INO had a lower overall vision-related quality of life (median 89.9, interquartile range 12.8) compared to patients without an INO (median 91.8, interquartile range 9.3, p = 0.011). CONCLUSIONS: This study provides an accurate quantitative and clinically relevant definition of an INO in MS. This infrared oculography-based INO standard will require prospective validation. The high prevalence of INO in MS provides an anatomically well described and accurately quantifiable model for treatment trials in MS.

The treatment of ocular hypotony after trabeculectomy with a scleral lens: A case series.

PURPOSE: Ocular hypotony after trabeculectomy may be treated medically, surgically and with a tamponade. Three cases are reported in which a scleral lens was applied to treat ocular hypotony after mitomycin C (MMC) augmented trabeculectomy. METHODS: In this retrospective case series the records of three eyes of three patients who developed ocular hypotony after they had undergone trabeculectomy augmented with MMC were evaluated. The patients were between 11 and 69 years of age and the intraocular pressure (IOP) after surgery ranged between 3 and 6 mmHg. All three patients showed a negative Seidel test; one had suspected hypotonic maculopathy and one had a collapsed anterior chamber. After unsuccessful treatment with large bandage lenses all three patients were subsequently fitted with a scleral lens. The scleral lens was fitted to fully cover and compress the bleb. Scleral lenses were worn continuously with a check-up after one night of wear and subsequent check-ups when needed. One patient continued to wear the scleral lens for a further 6.5 months on a daily wear basis. RESULTS: In all three eyes the IOP was higher after wearing the scleral lens. Two patients stopped wearing the scleral lens after the IOP was stable. One patient developed a cataract; the cataract surgery was combined with a bleb revision and scleral lens wear was therefore discontinued. DISCUSSION: The scleral lens might be a useful tool in the treatment of ocular hypotony after trabeculectomy augmented MMC surgery. The effect of the scleral lens on the ocular pressure is unpredictable. Caution is advised in vulnerable corneas due to risk factors such as hypoxia and infection. Further research is warranted to establish the safety of the procedure, the patient selection and the overall success in a larger patient group.

Saccadic fatigability in the oculomotor system.

BACKGROUND: Fatigue is one of the most common and disabling symptoms in multiple sclerosis (MS), but challenging to quantify. This prospective study investigated if repeated saccadic eye movements enable measurement of oculomotor fatigability and can reflect on perceived fatigue in MS. METHODS: A standardized infrared oculography protocol (DEMoNS) was used for quantifying saccades in MS patients and healthy controls which included a first and a repeated pro-saccadic task (FPT and RPT). Saccadic peak velocity, latency, gain, area under the curve (AUC) and peak velocity divided by amplitude (Pv/Am) were calculated in both tasks. Perception based fatigue was assessed using the Checklist Individual Strength and the Neurological Fatigue Index (NFI). Linear regression models were used for assessing the relation between saccadic parameters and perceived fatigue. RESULTS: This study included 181 MS patients and 58 healthy controls subjects. From FPT to RPT, there were significant changes in saccadic parameters. Latency of both tasks was significantly related to NFI summary score (FPT: ß = 0.022, p = .049, RPT: ß 0.023, p = .021). These relationships were weakened after adjustment for Expanded Disability Status score (p > .05). There was however no significant group difference in changes in saccadic parameters. CONCLUSIONS: This study presents an objective and reproducible method for measuring saccadic fatigability. Saccadic fatigability was found to be of limited use in MS, and should be tested in conditions affecting ocular muscles or the neuromuscular junction.

A standardized protocol for quantification of saccadic eye movements: DEMoNS.

OBJECTIVE: Quantitative saccadic testing is a non-invasive method of evaluating the neural networks involved in the control of eye movements. The aim of this study is to provide a standardized and reproducible protocol for infrared oculography measurements of eye movements and analysis, which can be applied for various diseases in a multicenter setting. METHODS: Development of a protocol to Demonstrate Eye Movement Networks with Saccades (DEMoNS) using infrared oculography. Automated analysis methods were used to calculate parameters describing the characteristics of the saccadic eye movements. The two measurements of the subjects were compared with descriptive and reproducibility statistics. RESULTS: Infrared oculography measurements of all subjects were performed using the DEMoNS protocol and various saccadic parameters were calculated automatically from 28 subjects. Saccadic parameters such as: peak velocity, latency and saccade pair ratios showed excellent reproducibility (intra-class correlation coefficients > 0.9). Parameters describing performance of more complex tasks showed moderate to good reproducibility (intra-class correlation coefficients 0.63-0.78). CONCLUSIONS: This study provides a standardized and transparent protocol for measuring and analyzing saccadic eye movements in a multicenter setting. The DEMoNS protocol details outcome measures for treatment trial which are of excellent reproducibility. The DEMoNS protocol can be applied to the study of saccadic eye movements in various neurodegenerative and motor diseases.

Straylight effects with aging and lens extraction.

PURPOSE: To assess possible gains and losses in straylight values among the population to consider straylight as added benefit of lens extraction. DESIGN: In this cross-sectional design, data from a multicenter study on visual function in automobile drivers were analyzed. METHODS: On both eyes of 2,422 subjects, visual acuity (logarithm of the minimum angle of resolution [logMAR] in steps of 0.02 log units), straylight on the retina (psychophysical compensation comparison method), and lens opacity (slit-lamp scoring using the Lens Opacities Classification System III [LOCS III] system) were determined. Three groups were defined: 220 pseudophakic eyes, 3,182 noncataractous eyes (average LOCS III score, <1.5), and 134 cataractous eyes (average LOCS III score, >3.0). RESULTS: Noncataractous straylight values increases strongly with age as: log(s) = constant + log(1 + (age / 65)(4)), doubling by the age of 65 years, and tripling by the age of 77 years. Population standard deviation around this age norm was approximately 0.10 log units. The cataract eyes (in this active driver group) had relatively mild straylight increase. In pseudophakia, straylight values may be very good, better even than in the noncataract group. Visual acuity and straylight were found to vary quite independently. CONCLUSIONS: Lens extraction holds promise not only to improve on the condition of the cataract eye, but also to improve on the age-normal eye. Lens extraction potentially reverses the strong age increase in straylight value, quite independently from visual acuity.

Posterior scleritis in a 7-month-old infant.

This article describes a 7-month-old infant with posterior scleritis, diagnosed on the basis of B-scan ultrasonography and computed tomography. The patient was initially diagnosed with preseptal cellulitis and endophthalmitis. Posterior scleritis should be considered in the differential diagnosis of acute orbital inflammation in children younger than 1 year.

[Unilateral blindness following a non-surgical rhinoplasty with filler]. / Eenzijdige blindheid na een neuscorrectie met filler.

BACKGROUND: A rare but known adverse event following a cosmetic filler treatment is unilateral blindness. In the Netherlands, this complication has not been reported in a patient before. CASE DESCRIPTION: A 26-year-old woman developed unilateral blindness after undergoing a cosmetic treatment of the dorsum nasi in which hyaluronic acid was used as filler. The blindness was caused by backflow of the filler via the ophthalmic artery into the carotid internal artery. CONCLUSION: There is no proven effective treatment for this adverse event. Therefore prevention is of great importance. This requires knowledge of the anatomy of the facial blood vessels and a well-developed injection technique.

Reliability of the compensation comparison stray-light measurement method.

The compensation comparison (CC) method is a psychophysical technique to measure retinal stray light. It uses a two alternative forced choice (2AFC) measurement paradigm. The 25 binary (0 and 1) responses resulting from the 2AFC test are analyzed using maximum likelihood estimates. The likelihood function is used to give two quantities: the most likely stray-light level of the eye under investigation, and the accuracy of this estimate [called expected standard deviation (ESD)]. The CC method is used in 2422 subjects of the GLARE study. Each eye is tested twice to allow analysis of measurement repeatability. Furthermore, the large amount of responses is used to evaluate the shape of the psychometric function, for which a mathematical model is used. The shape of the psychometric function found by averaging the 0 and 1 responses fit well to the model function. Data sorted according to ESD show differences in the shape of the psychometric function between good and bad observers. These different shapes for the psychometric function are used to reanalyze the data, but the stray-light results remain virtually identical. ESD proves to be an efficient tool to detect unreliable measurements. In clinical practice, ESD may be used to decide whether to repeat a measurement.

Measurement of stray light and glare: comparison of Nyktotest, Mesotest, stray light meter, and computer implemented stray light meter.

AIM: To evaluate the properties of devices for measuring stray light and glare: the Nyktotest, Mesotest, "conventional" stray light meter and a new, computer implemented version of the stray light meter. METHODS: 112 subjects, divided in three groups: (1) young subjects without any eye disease; (2) elderly subjects without any eye disease, and (3) subjects with (early) cataract in at least one eye. All subjects underwent a battery of glare and stray light tests, measurement of visual acuity, contrast sensitivity, refraction, and LOCS III cataract classification. Subjects answered a questionnaire on perceived disability during driving. RESULTS: Repeatability values were similar for all glare/stray light tests. Validity (correlation with LOCS III and questionnaire scores), discriminative ability (ability to discriminate between the three groups), and added value (to measurement of visual acuity and contrast sensitivity) were all superior for both stray light meters. Results of successive measurements are interrelated for the conventional but not the new stray light meter. This indicates a better resistance to fraud for the latter device. CONCLUSIONS: The new computer implemented stray light meter is the most promising device for future stray light measurements.

Eye torsion associated with disparity-induced vertical vergence in humans.

Recently, Enright described an unexpected association between disparity-induced vertical vergence and cycloversion (conjugate eye torsion) [Enright (1992) Vision Research, 415, 279]. The present experiments were performed to verify these findings and investigate the nature of this association. We presented subjects with a dichoptic image of concentric circles in which a step in vertical disparity of 1 deg was introduced. After 4 sec the disparity was eliminated. Eye movements were measured with scleral coils. We confirmed Enright's findings in that a left-over right vertical vergence was associated with levo-cycloversion (upper poles towards left shoulder) and vice versa. The size of the cycloversion and the vertical vergence were in the same range. In addition we found that part of the cycloversion response was in the form of a torsional nystagmus and that the relative contribution of the left and right eyes was independent of the horizontal gaze angle. These additional findings are in conflict with the hypothesis, offered by Enright, that the association is caused by a bilateral activity of the superior oblique muscles.

Visually induced cycloversion and cyclovergence.

Binocular cyclorotatory (torsional) eye movements in response to visual patterns, which oscillated sinusoidally in the frontal plane, were recorded with scleral induction coils in human subjects. Conjugate cycloversion and disjunctive cyclovergence were directly compared by in-phase and out-of-phase oscillation of the same pattern. Stimulus motion had a frequency of 0.2 Hz and amplitudes of 2-8 deg. Both response types had a similar and low gain (about 0.2 averaged over all subjects). Cycloversion showed no time lag, while cyclovergence lagged by about 600 msec. Non-fusible patterns were effective in eliciting cycloversion, but not cyclovergence. Apart from this, the nature of the pattern (randomly distributed dots, regular rows of dots, horizontal or vertical grating, Julesz stereogram or images with a pictorial significance) had only the slightest effect on the magnitude of the responses.

Binocular eye orientation during fixations: Listing's law extended to include eye vergence.

Any eye position can be reached from a position called the primary position by rotation about a single axis. Listing's law states that for targets at optical infinity all rotation axes form a plane; the so-called Listing plane. Listing's law is not valid for fixation of nearby targets. To document these deviations of Listing's law we studied binocular eye positions during fixations of point targets in the dark. We tested both symmetric (targets in a sagittal plane) and asymmetric vergence conditions. For upward fixation both eyes showed intorsion relative to the position that would have been taken if each eye followed Listing's law. For downward fixation we found extorsion. The in- or extorsion increased approximately linearly with the vergence angle. The direction of the Listing axis and the turn angle about this axis can be described by rotation vectors. Our observations indicate that for fixation of nearby targets the rotation vectors of the two eyes become different and are no longer located in a single plane. However, we find that it is possible to decomose the rotation vector of each eye into the sum of a symmetric and an anti-symmetric part, each with its own properties. (1) The symmetric part is associated with eye version. This component of the rotation vector is identical for both eyes and lies in Listing's plane. In contrast to the classical form of Listing's law, this part of the rotation vector lies in Listing's plane irrespective of the fixation distance. (2) The anti-symmetric part of the rotation vector is related to eye vergence. This component is of equal magnitude but oppositely directed in each eye. The anti-symmetric part lies in the mid-sagittal plane, also irrespective of fixation distance. For fixation of targets at optical infinity the anti-symmetric part equals zero and the eye positions obey the classical form of Listing's law. Thus, the symmetric and anti-symmetric parts of the rotation vectors are restricted to two perpendicular planes. Combining these restrictions in a model, with the additional restriction that the vertical vergence equals zero during fixation of point targets, we arrive at the prediction that the cyclovergence is proportional to the product of elevation and horizontal vergence angles. This was well born out by the data. The model allows to describe the binocular eye position for fixation of any target position in terms of the bipolar coordinates of the target only (i.e. using only three degrees of freedom instead of the six needed for two eyes).

Instability of ocular torsion during fixation: cyclovergence is more stable than cycloversion.

We investigated spontaneous variation of binocular torsion. Variation was expressed as SD of torsional eye positions measured over periods up to 32 sec. Subjects viewed a single dot target for periods of 32 sec. In half of the trials a large random-dot background pattern was superimposed on the dot. The movements of both eyes were measured with scleral induction coils. Spontaneous torsional movements were largely conjugate: cyclovergence was much more stable than cycloversion. This difference was not due to roll head movements. Stability of cyclovergence was improved by the background pattern. Although overall stability (SD of position) of cycloversion was unaffected by a background, the background induced or enhanced a small-amplitude torsional nystagmus in 3 out of 4 subjects. We hypothesize that the difference in stability of cycloversion vs cyclovergence reflects the greater importance of torsional retinal correspondence, compared to absolute torsional position. In two subjects we found evidence for the existence of cyclophoria, manifested by systematic shifts in cyclovergence caused by the appearance and disappearance of the background.

Eye torsion elicited by oscillating gratings: effects of orientation, wavelength and stationary contours.

We studied binocular cyclorotatory (torsional) eye movements in response to gratings that oscillated sinusoidally in a frontal plane. The square-wave gratings viewed by the right and left eye were presented and controlled separately to induce cycloversion and cyclovergence by oscillation in phase and out of phase. Eye movements were recorded with scleral induction coils. Stimulus oscillation frequency ranged from 0.125 to 1 Hz and the wavelength of the gratings ranged from 0.92 to 25.75 deg of visual angle. Cycloversion and cyclovergence gain were, on average, comparable in magnitude and decreased with increasing oscillation frequency. There was no consistent effect of the wavelength on the magnitude of the responses. In general, responses were considerably higher to gratings that were oriented horizontally than to those oriented vertically. This anisotropy was present both in cycloversion and cyclovergence. It was enhanced in a larger sized stimulus and by presenting stationary, orthogonal contours (mimicking a "shear" movement), but it was not consistently influenced by wavelength. Cyclovergence showed a phase lag, which increased with oscillation frequency but which was independent of wavelength. In contrast, cycloversion showed a slight phase lead which was independent of both oscillation frequency and wavelength.

Excess cyclovergence in patients with intermittent exotropia.

Recently, we developed a model of binocular fixation. This model predicts the amount of cyclovergence as a function of target elevation and horizontal target vergence. The prediction derives from the assumption that version and vergence add linearly and that the eye positions are constrained in three respects: (1) the foveae of the two eyes are directed towards the target, (2) the version component follows Listing's law, i.e. cycloversion, and horizontal and vertical version are not independent, (3) the vergence component is restricted to a plane approximately perpendicular to Listing's plane, i.e. horizontal, vertical and torsional vergence are not independent. The version and the vergence components are characterized by a common primary direction for the two eyes. We applied this model to data of patients with intermittent exotropia. In two patients with an amblyopic eye we found that the common primary direction rotates towards the amblyopic eye. In the third patient, not suffering from amblyopia, the common primary direction was practically straight ahead. In all three patients, cyclovergence angles were larger than those found in normal subjects. We found that the increased cyclovergence was compatible with our model for normal subjects if an offset on the horizontal vergence was given. This offset represents the additional convergence effort required in these patients to overcome the exodeviation of the eyes. According to our model the increased horizontal vergence effort results in excess cyclovergence. The relation between horizontal vergence and cyclovergence offers a new method for measuring the angle of exotropia.

Asymmetrical vertical phorias indicating dissociated vertical deviation in subjects with normal binocular vision.

We measured the symmetry of phoria angles in six normal subjects. Subjects were selected on the basis of good visual acuity and stereopsis, normal binocular eye alignment and, apart from mild refraction errors, absence of ocular abnormalities. They were instructed to look at a word on a reading chart at 2 m distance. Each measurement consisted of five subsequent intervals of 5 s duration. During these five intervals viewing was binocular, with the right eye only, binocular, with the left eye only, and binocular, respectively. Each experiment consisted of twelve measurements. Eye movements were measured with scleral coils suited for measuring in horizontal, vertical and torsional directions. Five out of six subjects displayed an asymmetrical vertical phoria; one subject showed an alternating hyperphoria; four displayed a left over right vertical phoria that was largest for left eye occlusion. Only one subject showed a symmetrical vertical phoria. Both the size of the vertical phorias and the size of the asymmetries in these vertical phorias were very small: on average 0.16 +/- 0.01 and 0.17 +/- 0.01 degree, respectively. The direction of the vertical phoria asymmetries (the largest left over right was found with left eye occlusion) and the fact that asymmetries were found more often in vertical than horizontal and torsional phorias suggest that these asymmetries are related to dissociated vertical deviation. These results suggest that dissociated vertical deviation, often observed in subjects with a disruption of binocular vision early in life, reflects the enhancement of a phenomenon that is present in normal subjects as well.

Relation between perceived driving disability and scores of vision screening tests.

AIM: To determine the relation between perceived driving disability and vision screening tests. METHODS: 93 subjects, aged 50 years and over, with binocular visual acuity of at least 20/80. Perceived driving disability (PDD) was assessed by a questionnaire. Subtracting daytime from night-time driving question scores revealed PDD at night (PDDN), subtracting scores of questions for driving in familiar places from those in unfamiliar places revealed PDD at unfamiliar places (PDDU). RESULTS: PDD was strongly related to visual acuity, contrast sensitivity and useful field of view (UFOV). Specific relations existed between PDDN and Nyktotests and Mesotests and between PDDU and UFOV. These associations were enhanced in a subset of subjects with better visual acuities. CONCLUSIONS: Vision screening tests correlate well with perceived driving disabilities, especially when a subtraction method is used in the questionnaire to reveal condition dependent disabilities. Additional tests for visual acuity are useful, especially in subjects with better visual acuity.