Oculomotor control in asymptomatic and recently diagnosed individuals with the genetic marker for Huntington's disease.

We compared oculomotor control among individuals in the early stages of Huntington's disease (HD), with that of individuals who are presymptomatic HD gene carriers (PSGC) and nongene carriers (NGC). The oculomotor testing paradigm included both traditional tests and a novel experimental procedure to assess visual scanning. Traditional tests elicited saccades, pursuit and optokinetic nystagmus (OKN). HD patients demonstrated marked delay in the initiation of volitional saccades (anti-saccade and memory-guided saccades), a reduced number of correct volitional saccades, reduced velocity of saccades, and a decreased OKN gain. We also studied visual scanning while the participants completed the Digit Symbol Subscale of the Wechsler Adult Intelligence Survey-Revised (WAIS-R). The HD participants demonstrated an abnormal gaze strategy, which may be associated with attention and/or planning deficits. Differences between the PSGC and NGC groups were only observed for two measures: PSGC had a decreased number of memory-guided saccades and a subtle delay in the initiation of volitional saccades. Our results suggest that oculomotor measures are a sensitive biomarker in the early stage of HD and demonstrate that the combination of more traditional oculomotor tests with visual scanning tests is useful in the evaluation of visual performance.

Response of saccadic eye movements to alcohol in African American and non-Hispanic white college students.

BACKGROUND: The primary goal of this study was to evaluate how race and sex interact with the effects of a moderate dose of alcohol on different ocular control subsystems in African American (AA) and non-Hispanic white American (WA) college students. METHODS: Horizontal visually guided (VG) saccades and antisaccades (AS) of 80 young adult, healthy, AA and WA college students were recorded with an infrared system. Subjects ingested 10 aliquots of ethanol at 3 min intervals, with the aggregate dose precalculated to yield a peak breath alcohol concentration (BrAC) of 80 mg%. Data from the measures performed at baseline and the ascending and descending limbs of the BrAC at approximately 65 mg% were compared across race and sex by multivariate analysis of variance. A no-alcohol control session, performed in 20 of the subjects, documented test-retest reliability of the VG and AS measurements. RESULTS: Both AA and WA groups demonstrated slowing of AS and VG saccades after alcohol administration, but there was no significant effect of 65 mg% alcohol on VG accuracy or AS errors. AS latency recovered toward baseline values, whereas the slowing of VG latency/velocity progressed, during alcohol exposure. There were significant differences between AA and WA groups in the time course of VG latency after alcohol but not in most other dependent measures. No significant effects for sex were observed in any of the saccade measures. The faster disappearance of alcohol in WA compared with AA was replicated, and some measures demonstrated a significant, albeit small, negative correlation between the alcohol disappearance rate and impairing effects of alcohol on saccades. CONCLUSIONS: Prolonged latencies and unchanged percentage of errors reflect a differential effect of alcohol on neural function in specific areas (parietal eye field, superior colliculus, and frontal eye areas). Race may interact with the effect of ethanol on saccadic eye movements in a college student population.

The Eye Book of Master Peter of Spain--a glimpse of diagnosis and treatment of eye disease in the Middle Ages.

Peter Hispanus, who became Pope John XXI, wrote a book about eye diseases and their treatment in the 13th century. De Oculis was not a scholarly treatise about eye diseases, but a manual intended for general physicians. Nevertheless, Latin copies were made into the 16th century, indicating its influence and importance. We present the first published English translation of De Oculis, based on a synthesis of the medieval Latin manuscripts and a German translation from the 19th century. The sources of Peter's understanding of the causes and treatment of eye diseases were the more scholarly and complete treatises by Greek and Arab writers. Many of the diseases described then cannot be correlated precisely with ophthalmic disorders known to us today because of the limited understanding of anatomy, function and pathophysiology that existed. However, De Oculis provides us with a glimpse of the practice of medicine in the Middle Ages.

Papilledema and obstructive sleep apnea syndrome.

OBJECTIVES: To characterize the pathogenesis and clinical features of optic disc edema associated with obstructive sleep apnea syndrome (SAS). METHODS: A series of 4 patients with SAS and papilledema (PE) underwent complete neuro-ophthalmologic evaluation and lumbar puncture. In 1 patient, continuous 24-hour intracranial pressure (ICP) monitoring was also performed. RESULTS: All 4 patients had bilateral PE that was asymmetric in 2. Three patients had optic nerve dysfunction, asymmetric in 1, unilateral in 2. Daytime cerebrospinal fluid pressure measurements were within normal range. Nocturnal monitoring performed in one patient, however, demonstrated repeated episodes of marked ICP elevation associated with apnea and arterial oxygen desaturation. CONCLUSIONS: We propose that PE in SAS is due to episodic nocturnal hypoxemia and hypercarbia resulting in increased ICP secondary to cerebral vasodilation. In these individuals, intermittent ICP elevation is sufficient to cause persistent disc edema. These patients may be at increased risk for developing visual loss secondary to PE compared with patients with obesity-related pseudotumor cerebri because of associated hypoxemia. The diagnosis of SAS PE may not be appreciated because daytime cerebrospinal fluid pressure measurements are normal and because patients tend to present with visual loss rather than with symptoms of increased ICP.

Eye movements in Parkinson's disease: before and after pallidotomy.

PURPOSE: To evaluate the effects of unilateral, stereotactic, posteroventral pallidotomy on saccadic eye movements in patients with Parkinson disease (PD). METHODS: Eye movements of 31 patients with moderate to advanced PD were recorded with an infrared system 1 month before and 3 months after pallidotomy. Two kinds of saccade tasks were used: saccade tasks for eliciting visually guided saccades and saccade tasks for eliciting internally mediated saccades (memory-guided, predictive, and anti-saccades). Latency, accuracy, peak velocity, and other parameters of saccades were evaluated. RESULTS: Internally mediated saccades were more impaired in patients with advanced PD compared with those with moderate PD. Pallidotomy did not affect visually guided saccades. After pallidotomy, the peak saccadic velocity of internally mediated saccades decreased. CONCLUSIONS: Hence, although pallidotomy has led to improvements in other motor functions, none were observed in saccadic responses. Rather, several modest decrements, below the level of clinical significance and all in internally mediated saccades, were observed.

Smooth-pursuit eye-movement deficits with chemical lesions in macaque nucleus reticularis tegmenti pontis.

Anatomic and neuronal recordings suggest that the nucleus reticularis tegmenti pontis (NRTP) of macaques may be a major pontine component of a cortico-ponto-cerebellar pathway that subserves the control of smooth-pursuit eye movements. The existence of such a pathway was implicated by the lack of permanent pursuit impairment after bilateral lesions in the dorsolateral pontine nucleus. To provide more direct evidence that NRTP is involved with regulating smooth-pursuit eye movements, chemical lesions were made in macaque NRTP by injecting either lidocaine or ibotenic acid. Injection sites first were identified by the recording of smooth-pursuit-related modulations in neuronal activity. The resulting lesions caused significant deficits in both the maintenance and the initiation of smooth-pursuit eye movements. After lesion formation, the gain of constant-velocity, maintained smooth-pursuit eye movements decreased, on the average, by 44%. Recovery of the ability to maintain smooth-pursuit eye movements occurred over approximately 3 days when maintained pursuit gains attained normal values. The step-ramp, "Rashbass" task was used to investigate the effects of the lesions on the initiation of smooth-pursuit eye movements. Eye accelerations averaged over the initial 80 ms of pursuit initiation were determined and found to be decremented, on the average, by 48% after the administration of ibotenic acid. Impairments in the initiation and maintenance of smooth-pursuit eye movements were directional in nature. Upward pursuit seemed to be the most vulnerable and was impaired in all cases independent of lesioning agent and type of pursuit investigated. Downward smooth pursuit seemed more resistant to the effects of chemical lesions in NRTP. Impairments in horizontal tracking were observed with examples of deficits in ipsilaterally and contralaterally directed pursuit. The results provide behavioral support for the physiologically and anatomic-based conclusion that NRTP is a component of a cortico-ponto-cerebellar circuit that presumably involves the pursuit area of the frontal eye field (FEF) and projects to ocular motor-related areas of the cerebellum. This FEF-NRTP-cerebellum path would parallel a middle and medial superior temporal cerebral cortical area-dorsolateral pontine nucleus-cerebellum pathway also known to be involved with regulating smooth-pursuit eye movements.

Neuro-ophthalmic, radiographic, and pathologic manifestations of adult-onset Alexander disease.

A 61-year-old woman had a 3-year history of imbalance. Eye movement studies revealed square-wave jerks, gaze paretic nystagmus, rebound nystagmus, impaired smooth pursuit, impaired optokinetic nystagmus, and abnormal fixation suppression of vestibular nystagmus. A brain magnetic resonance imaging study showed extensive areas of increased signal from the middle cerebellar peduncles and dentate nuclei, which enhanced with gadolinium. Histopathological analysis of a needle biopsy specimen of the left cerebellar peduncle revealed diffuse gliosis in the presence of symmetrically distributed areas of demyelination. There were associated Rosenthal fibers. Clinicopathologic correlation supported a diagnosis of Alexander disease. An adult patient with a history of progressive imbalance, ocular motility abnormalities consistent with cerebellar and/or brainstem dysfunction, and diffuse, symmetric hyperintense magnetic resonance imaging signals in brainstem and cerebellar white matter should suggest a diagnosis of adult-onset Alexander disease.

Influences of chorion type on saccadic eye movements in twins.

PURPOSE: The influence of genetic and prenatal environmental factors on characteristics of saccadic performance were evaluated in young monozygotic (MZ) twins (8-19 years old) of known chorion type. METHODS: Saccadic eye movements were recorded using an infrared system. Saccadic latency, accuracy, and parameters of amplitude-peak velocity exponential equation (main sequence) were quantified. RESULTS: Intraclass correlations of saccadic parameters differed significantly from zero for monochorionic and dichorionic MZ twins. The within-pair mean squares were significantly less, and intraclass correlations were significantly higher in monochorionic than in dichorionic twins for latency and were similar for other saccadic parameters (accuracy, slope of main sequence, and peak velocity for 15 degrees saccades). CONCLUSIONS: These findings confirmed previous reports that saccadic parameters of MZ twins are significantly correlated and indicated that similarity of these parameters seen in MZ twins may be driven both by genetic and by prenatal environmental factors.

Effects of acupuncture on foveation characteristics in congenital nystagmus.

AIMS/BACKGROUND: To examine the effects of acupuncture at the sternocleidomastoid muscles on foveation characteristics in congenital nystagmus. METHODS: Six patients with congenital nystagmus (CN) received a series of treatments consisting of two needles inserted into each sternocleidomastoid, stimulated by tapping gently every 5 minutes, for 20 minutes per session. Their eye movements were recorded using scleral search coils and changes in their CN waveforms analysed at each point in the treatment. Changes in the stability and duration of foveation periods were examined. RESULTS: Four of the six patients showed improved foveation at the commencement of treatment; three maintained this response throughout the treatment period and after the needles were removed. In two, the CN waveform itself was modified. CONCLUSION: This study and others involving afferent stimulation to the neck and face suggest that projections from these areas to the reticular formation and vestibular nucleus may alter the behaviour of the pathophysiological mechanism underlying congenital nystagmus.

Ocular neuromyotonia: three case reports with eye movement recordings.

The objective of this article was to evaluate the etiologies, findings, and treatment of ocular neuromyotonia (ONM) in three case reports. The etiologies of ONM were determined by the histories, neuroradiologic tests, or biopsies. Clinical observations, videotaping, and electronic eye movement recordings documented the eye movement abnormalities. Intermittent diplopia developed several years after myelography with thorium dioxide (Thorotrast), radiation treatment for a pituitary tumor, and radiotherapy for medulloblastoma of the posterior fossa. All of the patients had intermittent, variable tropias that occurred spontaneously or were induced by eccentric gaze. One patient had a partial third nerve palsy, and another had a unilateral internuclear ophthalmoplegia (INO). ONM involved the paretic third nerve, extraocular muscles, and ipsilateral lateral rectus muscle in one patient, the paretic medial rectus muscle (INO) in one patient, a lateral rectus muscle (INO) in one patient, and a lateral rectus muscle in the last patient. Eye movement recordings were consistent with spasms of the involved muscles. Carbamazepine (Tegretol) abolished the ONM in two patients. The other patient had been taking carbamazepine for seizures and developed ONM when the dose was decreased. Increasing the dose abolished the ONM. ONM is an unusual cause of intermittent diplopia and strabismus, but its distinctive history and signs identify it easily. Damage to the peripheral cranial nerves might produce segmental demyelination, axonal hyperexcitability, and a self-perpetuating, reverberating circuit that causes spasms of the extraocular muscles.

Smooth pursuit in twins before and after alcohol ingestion.

PURPOSE: The influence of genetic factors on characteristics of smooth pursuit were evaluated in young adult monozygotic (MZ) and dizygotic (DZ) twins before and after the administration of a single dose of ethanol. METHODS: Sinusoidal pursuit was recorded using a scleral search coil at frequencies of 0.25 and 0.5 Hz before and after alcohol consumption. Pursuit gain, interval between saccades, saccadic accuracy, and saccadic amplitude were quantified. RESULTS: Alcohol consumption reduced pursuit gain and saccadic accuracy and increased the rate and amplitude of saccades. Before and after alcohol consumption, the intraclass correlations for MZ twins (rMZ) were highly significant for pursuit gain, interval between saccades, and saccade amplitude. Corresponding correlations for DZ twins (rDZ) were not significant. Heritability values were similar before and after alcohol ingestion. CONCLUSIONS: The disparity between rMZ and rDZ suggests either multiple gene interactions or common environmental influences for MZ twins, greater than those for DZ twins.

Smooth pursuitlike eye movements evoked by microstimulation in macaque nucleus reticularis tegmenti pontis.

1. Smooth pursuitlike eye movements were evoked with low current microstimulation delivered to rostral portions of the nucleus reticularis tegmenti pontis (rNRTP) in alert macaques. Microstimulation sites were selected by the observation of modulations in single-cell firing rates that were correlated with periodic smoothpursuit eye movements. Current intensities ranged from 10 to 120 microA and were routinely < 40 microA. Microstimulation was delivered either in the dark with no fixation, 100 ms after a fixation target was extinguished, or during maintained fixation of a stationary or moving target. Evoked eye movements also were studied under open-loop conditions with the target image stabilized on the retina. 2. Eye movements evoked in the absence of a target rapidly accelerated to a constant velocity that was maintained for the duration of the microstimulation. Evoked eye speeds ranged from 3.7 to 23 deg/s and averaged 11 deg/s. Evoked eye speed appeared to be linearly related to initial eye position with a sensitivity to initial eye position that averaged 0.23 deg.s-1.deg-1. While some horizontal and oblique smooth eye movements were elicited, microstimulation resulted in upward eye movements in 89% of the sites. 3. Evoked eye speed was found to be dependent on microstimulation pulse frequency and current intensity. Within limits, evoked eye speed increased with increases in stimulation frequency or current intensity. For stimulation frequencies < 300-400 Hz, only smooth pursuit-like eye movements were evoked. At higher stimulation frequencies, accompanying saccades consistently were elicited. 4. Feedback of retinal image motion interacted with the evoked eye movements to decrease eye speed if the visual motion was in the opposite direction as the evoked, pursuit-like eye movements. 5. The results implicate rNRTP as part of the neuronal substrate that controls smooth-pursuit eye movements. NRTP appears to be divided functionally into a rostral, pursuit-related portion and a caudal, saccade-related area. rNRTP is a component of a corticopontocerebellar circuit that presumably involves the pursuit area of the frontal eye field and that parallels the middle and medial superior temporal cerebral cortical/dorsalateral pontine nucleus (MT/MST-DLPN-cerebellum) pathway known to be involved also with regulating smooth-pursuit eye movements.

Saccadic characteristics of monozygotic and dizygotic twins before and after alcohol administration.

PURPOSE: To evaluate the degree of heritability in the latency, accuracy, and peak velocity of reflexive saccades in young adult monozygotic (MZ) and dizygotic (DZ) twins before and after the administration of a single dose of ethanol. METHODS: Saccades were recorded using a scleral search coil before and after alcohol consumption, and data were analyzed offline. Estimates of heritability based in intraclass correlations (ICCs) and using a maximum likelihood estimates of genetic variance were calculated for the saccadic measures made before and after alcohol, as well as for the changes in latency, accuracy, and velocity. RESULTS: Intraclass correlations for MZ twins (rMZ) were highly significant; those for DZ twins (rDZ) were not significantly different from zero. This disparity between rMZ and rDZ suggests either multiple gene interactions or in utero environmental differences in the MZ twins. Alcohol significantly prolonged latency, reduced accuracy, and lowered peak velocity. Although the changes after alcohol were not significant, heritability values increased in all three measures after alcohol administration. CONCLUSIONS: Latency, accuracy, and peak velocity appear to be controlled by multiple genes or to depend on prenatal environmental factors. Even a single low dose of alcohol appeared to enhance heritability measures. Differences seen between ICCs for latency, accuracy, and velocity after alcohol administration suggest that developmental control of the neural mechanisms underlying each measure may vary.

Intermittent diplopia and strabismus caused by ocular neuromyotonia.

PURPOSE: Two cases illustrate the symptoms, signs, etiologies, and treatment of ocular neuromyotonia (ONM). METHODS: The histories, neuroradiologic tests, and/or biopsy revealed the etiologies of ONM in both patients. Clinical observations, videotaping, and electronic eye movement recordings documented the eye movements. RESULTS: A 72-year-old man with chronic arachnoiditis following myelography with thorium dioxide (Thorotrast) developed intermittent diplopia and a partial right third nerve palsy. Left gaze induced spasm of the right medial rectus. Right gaze produced right lateral rectus spasm. A 66-year-old woman, who had radiation treatment for a pituitary tumor and acromegaly, had intermittent spasm of the left medial rectus muscle and left esotropia. The episodes occurred spontaneously and were induced by right gaze. A left internuclear ophthalmoplegia was also found. Carbamazepine (Tegretol) abolished the ONM in both patients. CONCLUSIONS: Although ONM is an unusual cause of intermittent diplopia and strabismus, its distinctive clinical features identify it. Injury to the peripheral cranial nerves probably leads to segmental demyelination, axonal hyperexcitability, and a self-perpetuating, reverberating circuit, which causes spasms of the extraocular muscles.

Concordance of smooth pursuit and saccadic measures in normal monozygotic twin pairs.

Although the range of normal ocular motor performance is broad, little is known about the sources of variability. Genetic transmission of eye movement deficits has been described but such possible control of normal function has been little investigated. Characteristics of smooth pursuit and saccades can be examined for the degree of concordance in related individuals. In this pilot study, we studied saccades and pursuit in eight monozygotic (MZ) twin pairs. The statistical analysis of the data used the intraclass correlation of MZ twins (rMZ) to estimate what fraction the covariance of the twin pairs was of the population variance. All saccadic measures showed significant MZ correlations (p < 0.05). Smooth pursuit gains were even more highly correlated (p < 0.001). These results indicate considerable similarity within pairs of twins, particularly for horizontal smooth pursuit, and suggest that larger studies on monozygotic and dizygotic twins would be desirable, to help separate out the relative contributions of environmental and genetic factors.

Outcomes of optic nerve sheath decompression for nonarteritic ischemic optic neuropathy.

Efficacy of optic nerve sheath decompression (ONSD) in treating non-arteritic ischemic optic neuropathy (NAION) is not clear. We retrospectively analyzed the records of 91 patients with NAION, who were examined during a two-year period, and compared the final Snellen visual acuities of eyes treated with ONSD with those of eyes that did not have surgery. Seven of 18 eyes with ONSD (39%) demonstrated increased visual acuity of two or more lines; whereas 23 of 71 eyes without surgery (32%) had increased acuity. The ONSD group and no surgery group were further subdivided into eyes with progressive visual loss and nonprogressive visual loss. No statistically significant differences in visual outcome between groups were found. We did not find the high frequency of visual improvement that has been reported in some studies of ONSD for NAION.

Voluntary saccadic oscillations, resembling ocular flutter and opsoclonus.

Two human subjects, who had no signs of other neurologic disorders, produced large amplitude, to-and-fro saccadic oscillations. One subject generated these oscillations intentionally. Eye movement recordings by DC electro-oculography and/or magnetic scleral search coil showed that the movements were bursts of conjugate saccades in opposing directions with no intersaccadic intervals. They were multidirectional (horizontal, vertical, or oblique), had amplitudes up to 40 degrees and had linear or curvilinear trajectories. These characteristics are similar to those of ocular flutter and opsoclonus in patients with brainstem and/or cerebellar disorders. Our observations show that fixation instabilities resembling ocular flutter and opsoclonus can be produced voluntarily.

Current practices for monitoring ocular toxicity related to hydroxychloroquine (Plaquenil) therapy.

OBJECTIVE: Growing interest in aggressive early management of rheumatoid arthritis (RA) with hydroxychloroquine (alone or in combination with other immunomodulating drugs) is reason to review current practices for monitoring ocular toxicity in patients who take antimalarial therapy. METHODS: We surveyed by mail all ophthalmologists and rheumatologists in the State of Indiana about their practices in this regard. RESULTS: Twenty-nine of 31 rheumatologists (94%) responded. All but one recommended ophthalmologic examinations every 6 months and 41% would leave the choice of testing procedures to the ophthalmologist. Fifty percent had discontinued hydroxychloroquine because of a patient's failure to make and/or keep an appointment with the ophthalmologist. Of 213 ophthalmologists surveyed, 150 (70%) responded. Seventy-nine percent recommended semiannual examinations. Funduscopy, visual acuity, and color vision tests were reported to be performed routinely. Eleven of 13 retina specialists (85%), but only 25% of 127 general ophthalmologists, would obtain macular photographs (p < 0.001). Forty-two percent of general ophthalmologists, compared with 8% of retina specialists, would perform computerized perimetry (p < 0.001). Recognition of retinal hyperpigmentation as a classic sign was surprisingly low in both groups. Concurrent review of the medical records of 24 patients with RA or systemic lupus erythematosus showed extremely variable followup intervals for ophthalmologic examination; 7 of the 24 patients had no record of an ophthalmologic evaluation. CONCLUSION: As interest in the early, aggressive management of RA continues to grow, significant education needs to be devoted to the monitoring and diagnosis of ocular toxicity of hydroxychloroquine by both rheumatologists and ophthalmologists.

Visual loss and performance in blind athletes.

We examined the relationship between visual loss and athletic performance and evaluated the visual classification system used in the 1988 United States Association of Blind Athletes (USABA) Summer Games. Athletes were asked about their age, sex, training, years of participation in organized competition, age at onset of blindness and were given an ophthalmologic exam that included Snellen acuity, contrast sensitivity, and visual fields. In the speed track events, visual class,* sex, age, hours of training, and years participating were found to have a positive correlation with performance. Visual class and sex were significant predictors of performance in the intermediate distance events; visual class was the only significant predictor of performance in the long distance events. Visual class, sex, age, and hours of training were correlated with performance in the track and field (throwing) events. Weightlifting performance was influenced by age and sex. The most consistent predictor of performance in the swimming events was the number of hours training per week. Our results indicate that the current classification system for visual loss is useful for grouping athletes for competition.