Brain magnetic resonance imaging in acute optic neuritis. Experience of the Optic Neuritis Study Group.

OBJECTIVE: Changes in the brain on magnetic resonance images are common in patients with optic neuritis even when there is no other clinical evidence of multiple sclerosis. The current study was designed to determine systematically the prevalence of brain abnormalities on magnetic resonance images in the patients entered into the Optic Neuritis Treatment Trial. DESIGN: Prospective multicenter clinical trial. SETTING: Referral centers. PATIENTS AND METHODS: Brain magnetic resonance images from 418 patients with acute optic neuritis (77% women; mean age, 32.0 years) were evaluated at a central reading center with the use of a standardized classification system (ranging from 0 for normal to IV for most extensive changes). RESULTS: Of the scans, 40.9% were classified as grade 0, 10.8% as grade I, 9.1% as grade II, 6.7% as grade III, and 32.5% as grade IV. For patients with isolated (monosymptomatic) optic neuritis, 26.7% had two or more lesions. CONCLUSIONS: We found a lower prevalence of brain magnetic resonance imaging abnormalities in isolated optic neuritis than previous studies have reported. This likely is due to our study having a higher degree of standardization of patient inclusion criteria, which limited patient selection bias.

The pattern electroretinogram: a long-term study in acute optic neuropathy.

We report a 2-year prospective study of the electroretinographic response to reversal of checkerboard patterns (P-ERG) obtained in 63 eyes with acute optic nerve lesions. The aim of the study was to document the value of P-ERG regarding diagnosis and prognosis of four types of optic neuropathy: optic neuritis, compressive or hereditary optic atrophy, and traumatic optic neuropathy. We documented visual loss by neuro-ophthalmologic examination and recorded pattern-reversal visual evoked potentials (P-VEP). The initial P-ERG was normal to large- and medium-sized checks in 89% and the P-VEP abnormal in 94% of eyes with acute optic nerve lesions. Forty-six eyes were followed for up to 2 years. Two groups emerged. Group A (n = 17) gradually and permanently had significant reduction of the P-ERG to three separate check sizes. All 17 had no improvement in acuity better than 20/100, retained centrocecal scotomas, and developed optic atrophy. In group B (n = 29) the P-ERG remained within normal limits to one or more check sizes. Twenty-two of these eyes recovered acuity to 20/25 or better and had resolution of the field defect. The data showed that P-VEP was superior to P-ERG in diagnosis of acute and chronic optic nerve lesions. However, significant reduction of the b-wave of the P-ERG to three separate check sizes correlated closely with failure of visual recovery and the eventual development of severe optic atrophy, suggesting a prognostic value for P-ERG in optic neuropathy.

Electrophysiology versus psychophysics in the detection of visual loss in pseudotumor cerebri.

This study compared visual evoked potentials (VEP) and contrast sensitivity (CS) as methods of detecting visual loss in 15 women with acute onset of pseudotumor cerebri (PTC). A total of 24 out of 30 eyes (14 of 15 patients) had a visual disturbance. Neuro-ophthalmologic examination demonstrated abnormal Goldmann visual fields in 13 of 30 eyes. CS was abnormal in 18 eyes; VEP was abnormal in five eyes. Nine eyes had visual loss detected by CS only, five by perimetry only, and one had the VEP as the sole abnormality. CS was a valuable adjunct to perimetry in PTC whereas VEP was rarely helpful.

Optic neuritis: a prospective study.

We studied 20 patients with acute optic neuritis prospectively for 12 months. Visual fields, color vision, and VEPs to 15' checks were initially abnormal in all patients. Visual acuity was abnormal in 90% and contrast sensitivity in 95% of patients. We devised a graded visual impairment scale (GVIS) to include all visual functions tested. Complete recovery of visual function occurred in 65% of cases. Recovery in the majority of patients was rapid and complete within the first 2 months. In some patients, improvement continued over 6 months. The initial classification on the GVIS was significantly correlated with the final outcome. Patients initially classified as having moderate visual impairment recovered completely or improved to near normal vision. Sixty percent of patients initially classified as total or severe blindness had permanent visual impairment. VEP latency remained prolonged in 19 patients, even when their vision had returned to normal, and is a reliable indicator of resolved optic neuritis.

The predictive value of CSF oligoclonal banding for MS 5 years after optic neuritis. Optic Neuritis Study Group.

The predictive value of CSF oligoclonal banding for the development of clinically definite MS (CDMS) within 5 years after optic neuritis was assessed in 76 patients enrolled in the Optic Neuritis Treatment Trial. The presence of oligoclonal bands was associated with the development of CDMS (p = 0.02). However, the results suggest that CSF analysis is only useful in the risk assessment of optic neuritis patients when brain MRI is normal and is not of predictive value when brain MRI lesions are present at the time of optic neuritis.

Effect of decreased retinal illumination on simultaneously recorded pattern electroretinograms and visual-evoked potentials.

Sixteen normal subjects and three patients with optic neuritis were studied to determine the effect of decreased retinal illumination on simultaneously recorded pattern electroretinograms (PERG) and visual-evoked potentials (VEP). Using neutral-density filters (NDF), it was found that linear modeling is an excellent fit for VEP/PERG amplitudes and latencies as log functions of retinal illumination, both for individual eyes and averages of pooled data. Within narrow statistical limits, regression slopes show that mean PERG B-wave and VEP P100 latencies are affected almost identically by decreased illumination, leaving the mean retinocortical time (RCT) virtually unchanged. However, mean B-wave amplitude was greatly reduced at retinal illuminations at which P100 amplitude was unaffected. Of clinical significance was that these latency and amplitude effects were found in each eye tested, whether normal or pathologic. In particular, the RCT in normal subjects was never found to be statistically abnormal due to decreased retinal illumination, and it faithfully represented the optic nerve lesion in the patients with optic neuritis. This result was applied to a population of eight patients with uncomplicated cataracts. The significance of these results is discussed.

Really painful double vision.

A 67-year-old woman with a history of chronic headache and recent removal of two squamous cell lesions from her forehead presented with left facial pain and diplopia. A diagnosis of Tolosa-Hunt syndrome was made based on clinical presentation and imaging studies. When the patient did not respond to steroids, further studies were done, including biopsy, which revealed perineural spread of squamous cell carcinoma.

Long-term tamoxifen citrate use and potential ocular toxicity.

PURPOSE: To estimate the prevalence of abnormalities in visual function and ocular structures associated with the long-term use of tamoxifen citrate. METHODS: A single-masked, cross-sectional study involving multiple community and institutional ophthalmologic departments was conducted with a volunteer sample of 303 women with breast cancer currently taking part in a randomized clinical trial to determine the efficacy of tamoxifen (20 mg/day) in preventing recurrences. Participants included women who had never been on drug (n=85); women who had taken tamoxifen for an average of 4.8 years, then been off the drug for an average of 2.7 years (n=140); and women who had been on tamoxifen continuously for an average of 7.8 years (n=78). Women were evaluated by questionnaire, psychophysical testing, and clinical examination to determine any abnormalities in visual function and the comparative prevalences of corneal, lens, retinal, and optic nerve pathology. RESULTS: There were no cases of vision-threatening ocular toxicity among the tamoxifen-treated participants. Compared with nontreated participants, the tamoxifen-treated women had no differences in the activities of daily vision, visual acuity measurements, or other tests of visual function except for color screening. Intraretinal crystals (odds ratio [OR]=3.58, P=.178) and posterior subcapsular opacities (OR=4.03, P=.034) were more frequent in the tamoxifen-treated group. CONCLUSIONS: Women should have a thorough baseline ophthalmic evaluation within the first year of initiating tamoxifen therapy and receive appropriate follow-up evaluations.

Recent advances in neuro-imaging and the impact on neuro-ophthalmology.

Neuro-imaging is an essential part of the evaluation in patients with neuro-ophthalmologic disorders. Over the last two decades enormous advances in this area have been made allowing noninvasive evaluation of the orbit and brain. The idea of using nuclear magnetic resonance technology to produce images rather than the ionizing radiation of computed tomography (CT) began to emerge clinically in the late 1970s and early 1980s. Although the quality of early magnetic resonance imaging (MRI) scans was not much better than CT images, by the early 1990s, it became obvious that MRI had particular strength in identifying lesions in the posterior fossa, and demyelinating plaques. With advances in magnetic strength, computer software, surface coils, contrast medium, and more attention to the basic physics of magnet technology, the clarity of MR images improved dramatically. Recent advances in CT scanning (spiral and three-dimensional CT) and MRI (functional MRI and cine MRI) continue to affect significant changes in the discipline of neuro-ophthalmology. Furthermore, advances in MR angiography promise to allow excellent and noninvasive analysis of the cerebral vasculature. This review highlights the recent advances in neuro-imaging.

Improving the reliability of pattern electroretinogram recording.

The pattern electroretinogram (PERG) is a small electrical response of the retina to a reversing checkerboard pattern, usually less than 6 microV in amplitude. Unfortunately, the PERG can be obscured by artifacts such as blinks, eye movements, poor fixation, and amplifier saturation. Amplitude criterion artifact rejection systems found on commercial signal averagers eliminate large amplitude artifacts but are insensitive to small amplitude artifacts associated with amplifier saturation. Such saturation often occurs for several recording sweeps after large amplitude signals such as eye blinks are rejected. The presence of post-saturation artifacts complicates clinical PERG analysis. In this paper we describe procedures to remove these small amplitude artifacts from the PERG. These include computer selection of inputs for averaging and use of tracings with small input numbers to approximate PERG amplitudes. These procedures greatly reduce the variability of PERG amplitudes in the normal population, making PERG amplitude a more reliable clinical measure.

Ocular motility review for 1997-1998: part II.

Each year brings new scientific knowledge that builds on itself in a geometric fashion. Ocular motility basic and clinical neurosciences continue to advance with this accelerating pace. The years 1997 and 1998 brought new knowledge to the motility world. This review focuses on the clinical advances within this realm. Part I of this review appeared in the June 2000 (20:2) issue.

Ocular motility review for 1997-1998: part I.

Each year brings new scientific knowledge that builds on itself in a geometric fashion. Ocular motility basic and clinical neurosciences continue to advance with this accelerating pace. The years 1997 through 1998 brought new knowledge to the motility world. This review focuses on the clinical advances within this realm, presented in supranuclear to myopathic organization. Part II of this review will appear in the September 2000 (20:3) issue.

Use of pattern electroretinography to differentiate acute optic neuritis from acute anterior ischemic optic neuropathy.

The transient pattern electroretinogram (PERG) was recorded from 16 patients with acute optic neuritis and from 13 patients with acute non-arteritic anterior ischemic optic neuropathy (AION). All patients were tested within 35 days from the the onset of visual symptoms and all had significant central visual field abnormalities in their affected eyes as quantified by automated perimetry. Analysis of the PERGs showed that the amplitude of the N95 peak was abnormally reduced for each eye affected with AION while it remained normal in optic neuritis. No significant alteration in P50 amplitude was observed in either condition. The loss of N95 amplitude in AION was highly correlated with the average depth of visual field loss (in decibels) within a radius of 10 degrees of fixation. These results suggest that PERG could be used early in the course of optic neuropathy to distinguish optic neuritis from AION in those cases for which the diagnosis is still uncertain after the clinical examination.

The pattern electroretinogram: N95 amplitudes in normal subjects and optic neuritis patients.

Recent work has suggested that the N95 peak of the transient pattern electroretinogram (PERG) may be a more sensitive indicator of the late stages of retinal function prior to optic nerve activation than the P50 peak. In this report, we show that a new measure of N95 amplitude, based on digital filtering methods to identify a non-linear baseline before measurement, greatly reduced the amplitude variation in a population of 50 normal subjects when compared with two other plausible measures. We then used that new measure to follow the time course of N95 amplitudes in 12 optic neuritis patients. It was found that maintenance of a normal N95 amplitude at 6 months after onset of optic neuritis was always associated with excellent clinical recovery as measured by visual fields, acuity, presence or absence of an afferent pupil and optic atrophy, and contrast sensitivity (CS). Loss of N95 amplitude to below laboratory limits of normal was associated with abnormalities in these indicators of visual function. This study supports the idea that the N95 peak represents retinal ganglion cell function.

Visual impairment in hysteria.

We have reviewed the charts of 45 neuro-ophthamological patients diagnosed with 79 monocular visual field or visual acuity losses secondary to non-organic etiology. Our aim was to determine the percentage of patients that have improvement in vision. As part of the protocol, all patients had magnetic resonance images, pattern visual evoked potentials, and flash electroretinography in addition to complete neuro-ophthalmological examinations. A single physician performed both the initial and follow-up examinations of all patients. Thirty-three percent of these patients had visual field defects only, 62% had both visual field defects and visual acuity defects, and 5% had only visual acuity defects. After organic disease was ruled out, all were given a timetable for recovery and clear reassurance regarding their prognoses for visual recovery. Seventy-eight percent of these patients showed improvement or were normal, while 22% showed no improvement. Younger patients without obvious psychiatric disorder had better prognoses than older patients.

Breast cancer metastatic to the eye is a common entity.

Breast cancer metastatic to the eye is a common entity occurring in up to 30% of women with metastatic disease. The prevalence of this lesion is not appreciated because of the dominant clinical picture of metastases occurring in other organs. The diagnosis should be suspected in any women with a history of breast cancer and any visual symptoms, particularly metamorphopsia and scotomata. A thorough ophthalmologic evaluation, aided by ultrasonography, computed tomography, or magnetic resonance scanning, usually confirms the diagnosis. Early treatment with radiation therapy can alleviate symptoms and control local disease. The recognition and treatment of this disorder is important in maximizing the quality of life in patients with metastatic breast cancer, especially because newer treatment regimens prolong survival and thereby increase the chances for ocular metastasis.

The pattern visual evoked potential. A multicenter study using standardized techniques.

The peak latency of the pattern-reversal visual evoked potential is a sensitive measure of conduction delay in the optic nerve caused by demyelination. Despite its clinical utility, the pattern-reversal visual evoked potential has not previously been used in multicenter clinical trials, presumably because of difficulty in standardizing conditions between centers. To establish whether the pattern-reversal visual evoked potential could be adequately standardized for use as a measure in multicenter therapeutic trials for optic neuropathy or multiple sclerosis, stimulus and recording variables were equated at four centers and pattern-reversal visual evoked potentials were recorded from 64 normal subjects and 15 patients with resolved optic neuritis. Results showed equivalent latency and amplitude data from all centers, suggesting that stimulus and recording variables can be satisfactorily standardized for multicenter clinical trials. N70 and P100 peak latencies and N70-P100 interocular amplitude difference were sensitive measures of resolved optic neuritis.