Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis.

Sarcoidosis may cause severe ventilatory impairment requiring corticosteroid treatment. Chloroquine (CQ) can be an effective treatment for lung sarcoidosis with few side effects, but has not been accepted as standard therapy. We investigated the benefits of prolonged CQ therapy in 23 symptomatic patients with biopsy-proven pulmonary sarcoidosis (duration, >/= 2 yr). Patients were initially treated for 6 mo with CQ, 750 mg/d, tapering every 2 mo to 250 mg/d. Eighteen patients were then randomized to either a Maintenance group (CQ, 250 mg/d) or to an Observation group (no CQ). After the initial treatment, significant improvement was observed in symptoms, pulmonary function, angiotensin-converting enzyme, and lung gallium scan. Patients randomized to the Maintenance group showed a slower decline in pulmonary function (FEV1, 51.4 +/- 28.2 ml/yr [Maintenance] versus 196.3 +/- 33.4 ml/yr [Observation], p < 0.02) and had fewer relapses: 2 of 10 patients in the Maintenance group at 29.5 +/- 4.9 mo versus 6 of 8 patients in the Observation group at 15.5 +/- 2.9 mo. Adverse effects were seen mainly during high-CQ dosage. We conclude that CQ should be an important consideration for the treatment and maintenance of chronic pulmonary sarcoidosis.

Chronic encephalitis (Rasmussen's syndrome) and ipsilateral uveitis.

Two children are reported with acute uveitis during the early progressive phase of chronic encephalitis (Rasmussen's syndrome). In both children, the side of the uveitis was ipsilateral to the side of cerebral inflammation, although in 1 child there were milder inflammatory changes in the contralateral eye. This association adds weight to the viral hypothesis of chronic encephalitis and raises the possibility of primary ocular infection and neurotropic spread to the brain.

Computed tomography and magnetic resonance imaging of an infiltrative lesion of the anterior visual pathways.

Infiltrative lesions of the optic chiasm and optic nerves are uncommon. The authors report such a case and discuss the differential diagnosis, paying particular attention to imaging. In the reported case high-resolution computed tomography and magnetic resonance imaging revealed thickening of the optic chiasm and intracranial optic nerves, a pattern characteristic of an inflammatory or neoplastic process.

Ocular pseudomyasthenia or ocular myasthenia 'plus': a warning to clinicians.

Myasthenia gravis (MG) commonly presents with weakness and fatigability of the lids and extraocular muscles, which respond to treatment with anticholinesterase medication. However, certain intracranial mass lesions may mimic these features of MG; alternatively, MG may mask the signs of a coexistent intracranial mass. We describe 8 patients originally diagnosed as having MG by knowledgeable clinicians, in whom an intracranial lesion instead of, or in addition to, MG was later identified. The lesions included parasellar tumors and aneurysms. In patients presenting with clinical features of ocular MG, it is therefore essential to establish a definite diagnosis of MG, to exclude other possible causes of "pseudomyasthenia," and to exclude other diseases that might be masked by coexisting myasthenic weakness. We recommend that patients with clinical features of MG limited to the ocular or cranial musculature be thoroughly evaluated for intracranial mass lesions, using CT or MRI if warranted.

Irregular pupil cycling as a characteristic abnormality in patients with demyelinative optic neuropathy.

We used an infrared videopupillometer combined with an electronic circuit that regulated the retinal light level as a function of pupil area to assess the regularity of pupil cycling in normal subjects and in patients with known abnormalities in the pupil light reflex pathways. The light stimulus was turned on whenever pupil area exceeded a preset value. Two types of abnormalities were observed for patients with demyelinative optic neuropathy: a failure of the pupil to cycle despite a preserved pupillary response to a single light pulse; and, for those patients in whom cycling was possible, a characteristic intermittent irregularity in the amplitude of pupil cycling. These abnormalities were not seen in normal subjects or in patients with ischemic optic neuropathy, surgical lesions involving the optic chiasm, Adie's syndrome, or Horner's syndrome.

The pattern electroretinogram in optic nerve demyelination.

The pattern electroretinogram (PERG) is probably generated by the ganglion cell layer of the retina whose axons constitute the conductive fibres of the optic nerves. A study was undertaken of the PERG in a group of patients with clinically definite multiple sclerosis who had suffered optic nerve demyelination to assess the value of recording the PERG as a method for electrophysiological determination of optic nerve dysfunction. Pattern visual evoked potentials (PVEP) were simultaneously recorded, each eye being stimulated separately, and four different check sizes were used. Although individual patients showed PERG abnormalities the results as a group showed no significant difference from the normal population so far as latency or amplitude of the PERG was concerned. Thus we conclude that the PERG, while an interesting measurement, does not satisfactorily reflect optic nerve dysfunction. Further, our results indicate that it is not such a useful measure as the pattern visual evoked response for detecting optic nerve disease.

Ophthalmodynamometry revisited.

Ophthalmodynamometry was performed on 100 patients with amaurosis fugax or transient cerebral ischemic attacks to determine its value in identifying significant (over 50%) carotid stenosis as verified by angiography. Of three criteria for an abnormal result of ophthalmodynamometry a corrected systolic pressure of 70 mm Hg or less had the highest sensitivity (95%) and overall accuracy (88%) in identifying significant carotid stenosis. However, with the use of all three criteria, only one of which had to be met in an individual case, ophthalmodynamometry still identified significant carotid obstruction with 80% sensitivity, 78% accuracy and a false-positive rate of 25%. Thus, ophthalmodynamometry appears to be just as useful as any of the more expensive and complicated noninvasive tests for carotid stenosis currently available.

Arteriovenous malformations of the posterior cerebral hemispheres.

Arteriovenous malformations (AVMs) of the brain usually present with acute hemorrhage or epilepsy. Of 54 patients with AVMs limited to the posterior cerebral hemispheres some 60% had intermittent or acute visual symptoms. Most had homonymous hemianopia. Because of the possible neurologic consequences of an AVM it is important to distinguish the headaches and visual symptoms of this lesion from those of classic migraine, a more common condition. In this paper this differentiation and the pathogenesis of the symptoms are reviewed.

Flash electroretinogram abnormalities in patients with clinically definite multiple sclerosis.

We studied the flash electroretinograms (ERGs) of 105 patients with multiple sclerosis who were divided into four groups. The first group had no history or clinical evidence of optic nerve dysfunction, the second and third groups had either left or right optic nerve disease respectively, and the fourth group had historical or clinical evidence of bilateral optic nerve disease. Statistical analysis of the data using analysis of variance (ANOVA) showed that the group of patients with no history or clinical evidence of optic nerve disease had no significant difference from the control group for their peak b-wave implicit times but the other three groups were significantly delayed on the affected side(s). Using the Mann-Whitney U-test we found all four patient groups had significantly greater absolute interocular latency differences from the control group. The electroretinal contribution to flash VEP delay was also investigated. In those patients with unilateral or bilateral optic nerve disease we found that in 14-31% of those patients with flash VEP delay there was also abnormal prolongation of the ERG b-wave. These results confirm a high incidence of retinal dysfunction in multiple sclerosis patients and may suggest that transynaptic degeneration of retinal structures occurs in optic nerve demyelination. The significant absolute interocular latency difference in particular may provide another electrophysiological parameter to establish a diagnosis of multiple sclerosis in suspect cases.

Orientation-specific visual evoked potential deficits in multiple sclerosis.

Checkerboard pattern reversal visual evoked potentials (VEPs) have proved useful in the confirmation of optic nerve disease in patients with multiple sclerosis (MS). Recently evidence of orientation-specific loss in contrast sensitivity and the presence of orientation-specific visual evoked potential (VEP) deficits in MS patients has been obtained using sinusoidal gratings as stimuli. This study reports the presence of orientation-specific VEP delay in MS using the conventional checkerboard pattern presented in two orientations: normally oriented (check condition) or diagonally oriented (diamond condition). Peak latency values of the N70 and P100 components of the VEP were statistically analyzed using appropriate ANOVA and nonparametric statistics. As a group of MS patients showed significant VEP delays under check and diamond pattern conditions. However, individual subject analysis revealed that about 20% of the MS population show VEP delay to only one pattern orientation. It was shown that by including a diamond pattern condition the diagnostic yield of VEP delay in these clinically definite MS patients was increased 11% over that obtained with check stimulation alone.

Failure of suppression of post-caloric nystagmus by fixation.

One hundred and seven patients who had failure of fixation suppression (FFS) of their post-caloric nystagmus were studied. Most of them had other ocular motor abnormalities such as defective pursuit, gaze paretic and rebound nystagmus, and saccadic dysmetria. The presence of FFS was unrelated to the type of post-caloric response. The data from this study are compatible with the idea that FFS is a manifestation of a disturbance in the visual-vestibular interaction. While FFS alone is not a useful localizing sign, its presence is patients who are not taking drugs should lead to a search for neurological disease particularly in the posterior fossa.

Pattern ergs and check size: absence of spatial frequency tuning.

The pattern electroretinogram (PERG), whose genesis appears to depend upon intact retinal ganglion cells, is receiving attention from clinical electrophysiologists because of its possible value as an aid in the diagnosis of optic nerve disease. Until now there have been no published studies describing the PERG in a large normal population nor has the effect of check size been systematically investigated in normals. We have investigated peak latency, amplitude and interocular amplitude ratio of the P, Q and R-waves of the PERG and their relationship to several pattern visual evoked potential (PVEP) parameters. In 35 normal subjects simultaneous PERGs and PVEPs were recorded using four different check sizes. The study of these small amplitude waveforms was facilitated by digital subtraction of eye movement artefact. The distribution of normal control data is described and a clinical terminology for the PERG components is proposed.

An electroretinal and visual evoked potential study in Friedreich's ataxia.

We made an electroretinographic (ERG) and visual evoked potential (VEP) study of 12 patients with Friedreich's ataxia whose diagnosis was established using the Quebec diagnostic criteria. ERGs and VEPs were elicited to the same stimulating conditions. Flash evoked luminance changes and pattern-specific evoked potentials to check and diamond stimuli were used. Statistical analysis of the data was made using independent sample t-tests. Significant VEP delays were present under all test conditions. The presence of significant interocular and interhemispheric delays as well as evidence of abnormal temporal dispersion of the VEP response suggest there to be both diffuse anterior visual system disease and retrochiasmal involvement in Friedreich's ataxia. The implicit times of the ERG b-waves were statistically within normal limits but the waveforms were of low amplitude and deformed and there were significant interocular implicit time differences. These ERG results suggest there are retinal conduction abnormalities in Friedreich's ataxia which possibly play a role in the genesis of the abnormal VEPs.

Abnormal electroretinograms and visual evoked potentials in chronic papilledema using time-difference analysis.

Visual function is usually considered to be normal in papilledema. We report previously undescribed abnormalities in the electroretinograms (ERG) and visual evoked potentials (VEP) of two patients with chronic papilledema. The steady-state latencies of the ERG and VEP were calculated using time-difference analysis. The ERG was abnormal under both scotopic (slow) and photopic (fast) flicker conditions, but the VEP was abnormal only to fast flicker photopic stimulation. This may indicate a relative vulnerability of a high frequency signal system under conditions of raised intracranial pressure. The abnormalities resolved rapidly once the intracranial pressure had been normalised. The cause of the VEP and particularly the ERG abnormalities remains unknown.

Effect of timolol maleate on intraocular pressure and pupil cycle time in normal eyes.

One drop of 0.5% timolol maleate instilled into the normal eyes of four subjects produced a marked reduction of intraocular pressure that was maximal at 3 hours but not significant after 12 hours. Instillation of one drop a day for 30 days produced a reliable, maintained reduction of intraocular pressure in the treated eye. The pupil cycle time in both eyes was measured at least twice daily for 1 week before timolol treatment to assess the reproducibility of the test and then twice daily for the 30 days of treatment with timolol. The drug had no significant effect on the pupil cycle time. Measuring the pupil cycle time should afford the ophthalmologist a useful method of assessing the progress of glaucomatous damage to the optic nerve while the patient is undergoing treatment with timolol, an assessment that was not possible when patients were treated with pilocarpine.

Improved contrast sensitivity with antireflective coated lenses in the presence of glare.

Contrast sensitivity was measured to quantify the glare-reducing effects of antireflective coatings of magnesium fluoride on spectacle lenses. Experiments were conducted on four subjects, who judged contrast thresholds while wearing corrective spectacles with noncoated and then coated lenses in both the absence and the presence of a source of glare (back-scattered reflection from the posterior surface of their lenses). Glare substantially reduced contrast sensitivity at all spatial frequencies; although the reduction was greater at higher spatial frequencies ther was no shift in peak contrast sensitivity. The coated lenses enhanced contrast sensitivity in the presence of glare between 1.5 and 5 times compared with the noncoated lenses. In the absence of glare, contrast sensitivity was greater with coated lenses than with noncoated lenses.

Increased visual field area with antireflective coated lenses in the presence of glare.

Visual fields were charted with the Goldmann perimeter for five subjects wearing corrective spectacles with noncoated lenses and then lenses with antireflective coatings of mmagnesium fluoride in both the absence and the presence of a source of glare (back-scattered reflection from the posterior surface of their lenses). There was a greater reduction in temporal isopters than nasal isopters in the presence of glare with both types of lenses, but the coated lenses were superior to the noncoated lenses in reducing the effect of glare on the visual field area.

Task dependent variations of ocular lateropulsion in Wallenberg's syndrome.

The eye movements of a patient with a left lateral medullary infarct (Wallenberg's syndrome) were recorded using the scleral search coil in magnetic field technique. When asked to look at spontaneously appearing targets, saccades to the left were generally accurate but those to the right reached the target by multiple step refixation saccades. Large amplitude rightward saccades were possible between two continuously visible targets or when making voluntary saccades in the dark. Vertical saccades, up or down, between spontaneously appearing targets were always associated with a leftward eye movement (lateropulsion). Voluntary vertical saccades between continuously visible targets showed that upward movements had left lateropulsion but downward movements were normal. Vertical voluntary saccades in the dark were oblique, upward saccades showing left lateropulsion and downward saccades rightward deviation. The aberrant horizontal components of normal oblique saccades. Possibly impaired assessment of verticality with incorrect eye position information produced by the infarct accounts for the lateropulsion in saccades in Wallenberg's syndrome.

Multiple regression analysis of diagnostic predictors in optic nerve disease.

Demyelination is assumed to be the cause of the majority of cases of isolated optic neuritis. Because of the importance of establishing the presence of optic nerve dysfunction in patients suspected of having multiple sclerosis several new indices of optic nerve conduction have been reported including the visual evoked potential, the edge-light pupil cycle time, and the Pulfrich test. These measures purport to detect optic nerve dysfunction but with varying degrees of success. This study of 93 patients with clearly documented previous optic neuritis was conducted to determine the statistical relationship between these three measures and other clinical diagnostic indices for detection for previous optic nerve disease and the utility of the diagnostic predictors taken individually, and in combination. The other indices used were the presence of detectable optic atrophy, color vision defect and the presence of a relative afferent pupillary defect. The variables were submitted to linear stepwise multiple regression analysis which indicated that the presence of optic atrophy, defective color vision and prolonged pupil cycle time when used in combination provided the most useful diagnostic prediction of previous optic neuritis in this group of patients. The addition of visual evoked potentials, the Pulfrich test or presence of a relative afferent pupillary defect did not significantly increase predictive reliability.