Lars Frisén

Diagnosis and Grading of Papilledema in Patients With Raised Intracranial Pressure Using Optical Coherence Tomography vs Clinical Expert Assessment Using a Clinical Staging Scale

OBJECTIVES To compare and contrast 2 methods of quantitating papilledema, namely, optical coherence tomography (OCT) and Modified Frisén Scale (MFS). METHODS Digital optic disc photographs and OCT fast retinal nerve fiber layer (RNFL) thickness, fast RNFL map, total retinal thickness, and fast disc images were obtained in 36 patients with papilledema. Digital optic disc photographs were randomized and graded by 4 masked expert reviewers using the MFS. We performed Spearman rank correlations of OCT RNFL thickness, OCT total retinal thickness, and MFS grade from photographs. RESULTS OCT RNFL thickness and MFS grade from photographs correlated well (R = 0.85). OCT total retinal thickness and MFS grade from photographs had a similar correlation of 0.87. Comparing OCT RNFL thickness with OCT total retinal thickness, a slope of 1.64 suggests a greater degree of papilledema thickness change when using the latter. CONCLUSIONS For lower-grade abnormalities, OCT compares favorably with clinical staging of optic nerve photographs. With higher grades, OCT RNFL thickness processing algorithms often fail, with OCT total retinal thickness performing more favorably.

Acyclovir treatment of relapsing-remitting multiple sclerosis. A randomized, placebo-controlled, double-blind study.

Acyclovir treatment was used in a randomized, double-blind, placebo-controlled clinical trial with parallel groups to test the hypothesis that herpes virus infections are involved in the pathogenesis of multiple sclerosis (MS). Sixty patients with the relapsing-remitting form of MS were randomized to either oral treatment with 800 mg acyclovir or placebo tablets three times daily for 2 years. The clinical effect was investigated by an extensive test battery consisting of neurological examinations, neuro-ophthalmological and neuropsychological tests, and evoked potentials. Results were based on “intent-to-treat” data and the primary outcome measure was the exacerbation rate. In the acyclovir group (n = 30), 62 exacerbations were recorded during the treatment period, yielding an annual exacerbation rate of 1.03. The placebo group (n = 30) had 94 exacerbations and an annual exacerbation rate of 1.57. Thus, 34% fewer exacerbations were encountered during acyclovir treatment. This difference in exacerbation rate between the treatment groups was not significant (P = 0.083). However, this trend to a lower disease activity in acyclovir-treated patients was supported in subsequent data analysis. If the patients were grouped according to exacerbation frequencies, i.e. into low (0–2), medium (3–5) and high (6–8) rate groups, the difference between acyclovir and placebo treatment was significant (P = 0.017). Moreover, in a subgroup of the population with a duration of the disease of at least 2 years providing an exacerbation rate base-line before entry, individual differences in exacerbation rates were compared between the 2-year pre-study period and the study period in acyclovir-treated (n = 19) and placebo (n = 20) patients and acyclovir-treated patients showed a significant reduction of exacerbations (P = 0.024). Otherwise, neurological parameters were essentially unaffected by acyclovir treatment and there were no convincing signs of reduced neurological deterioration in the acyclovir group. This study indicates that acyclovir treatment might inhibit the triggering of MS exacerbations and thus suggests that acyclovir-susceptible viruses might be involved in the pathogenesis of MS. This possibility warrants further investigation.

Vigabatrin Visual Toxicity: Evolution and Dose Dependence

Summary:  Purpose: To investigate the prevalence and prognosis of visual field defects (VFDs) in epilepsy patients with and without vigabatrin (VGB) treatment; to investigate the possible relationship between VFDs and cumulative VGB dose, and to characterise the evolution of VFDs.

New, sensitive window on abnormal spatial vision: rarebit probing.

Clinical tests have a poor sensitivity to low to moderate degrees of neuro-visual damage, possibly because their test targets involve numerous receptive fields. A new test used briefly exposed microdots of high contrast. Multiple visual field areas were probed repeatedly, with ever-new microdot positions. Normal subjects responded to a median 96.0% of probes. Patients with different visual field defects missed larger numbers of probes within defects and the deeper the defects, the larger the number of misses. Patients with minor chiasmal lesions averaged 1.8 times larger defects in microdot perimetry than in high-pass resolution perimetry, indicating superior sensitivity to minor damage.

Contrast sensitivity in macular disease. A preliminary report.

Psychophysical measurements of contrast thresholds for sinusoidal gratings of variable frequency were made in normal controls and in patients with macular disease. Normal controls showed a U‐shaped contrast sensitivity function comparable with previous reports. Patients with relatively well conserved visual acuity showed a marked impairment in contrast sensitivity for targets of high and intermediate spatial frequencies, while patients with more advanced disease showed a pronounced impairment across a larger spectrum of frequencies. Our findings provide insight into the visual difficulties of daily life of patients with macular disease. The determination of contrast sensitivity seems to be an important and very sensitive tool for the detection of early disturbances.

High-pass resolution perimetry

Polyopia, visual perseveration in space, has been associated with seizure activity, afterimage formation, and the presence of visual field defects. It can be interpreted both as a positive and a negative visual phenomenon. A patient with polyopia associated with the acute onset of hemianopsia is presented. The phenomenon has been investigated objectively with a simple procedure. The polyopia was highly correlated to movement of the eyes into the hemianoptic visual field and to increased contrast but not duration of the stimulus. This type of polyopia could be the result of incomplete visual processing due to poor visuospatial localization in a hemianopic field.

EVOLUTION OF DESCENDING OPTIC ATROPHY

Fundus changes following severe trauma to the intracranial optic nerve were followed by means of serial fundus photography. The eye was completely blind. Little change was seen during the first 4 weeks. The retinal nerve fibre layer disappeared gradually during weeks 4 to 8. At the same time the retinal vessels turned narrow, and vascular pseudo‐sheathing appeared close to the optic disc. Disc pallor was not maximal until the 12th week, when the peripapillary retina also had acquired a mottled appearance.

Narrowing of the Retinal Arterioles in Descending Optic Atrophy: A Quantitative Clinical Study

Measurements were made on fundus photographs of the diameters of retinal arterioles in a series of cases with various nonvascular lesions of the anterior visual pathways, before and after the development of fundus signs of optic atrophy. A simple method was devised for reliable estimation of the diameter of the central retinal artery whenever this vessel could not be measured directly: this allowed comparisons to be made between different eyes, irrespective of individual variations in arteriolar branching patterns. Atrophy was consistently associated with a decrease in central retinal artery caliber, averaging 24% in eyes developing total optic atrophy, and 17% in eyes with hemi-atrophy. Normal controls showed a maximum side difference of 8%.

High-pass resolution perimetry and age-related loss of visual pathway neurons

Abstract The normal, age‐related decline of results of high‐pass resolution perimetry (HRP) predicts a loss of approximately 9 000 retino‐cortical neural channels per year of age, or about 1 channel each hour. Previously published counts of numbers of neurons in the optic nerve indicate a loss of approximately 5 000 neurons per year. The HRP results can be accounted for by postulating that neurons are lost at the same rate also in the geniculo‐striate visual pathway.

Asymptomatic visual loss in multiple sclerosis.

Abstract Visual disturbances are common in multiple sclerosis (MS) and often a result of acute demyelinating optic neuropathy. Careful examination of MS patients, who have never suffered optic neuritis, may also reveal asymptomatic visual loss. This type of silent disease activity was investigated by computerised resolution perimetry, which has the potential to reflect the percentage of functional retino-cortical neural channels. The time of onset and the evolution of asymptomatic visual loss was investigated. One approach was to retrospectively select patients who never had suffered acute optic neuritis from a closely monitored MS population and re-examine them again. Sixteen patients were identified and vision was evaluated during a period of 5.5–9 years of follow-up and compared with that in 14 healthy controls. The mean channel percentage of the MS group was 89 ± 19 % (SD) on entry into the study, compared with 110 ± 15 % (SD) of controls (p < 0.003). At termination of the study the mean percentage was essentially unchanged both in MS patients (87 ± 21 %, SD) and controls (110 ± 19 %, SD). The second approach was to test a group of 7 patients with MS or strongly suspected MS, with the same method, in close connection with their first clinical exacerbation. All cases lacked visual symptoms and none had previously had acute visual loss. Again, virtually all performed subnormally in the vision tests, and to the same degree as in the first group of patients. Results were compared with those obtained from 25 MS patients who had experienced one or more attacks of optic neuritis. Compared with controls the loss of functional retino-cortical neural channels was 20 % in patients without a previous history of optic neuritis and 30 % in patients who previously had experienced optic neuritis. We conclude that asymptomatic visual loss seems to be a universal feature of MS and has a substantial impact on the visual pathways, that it is present already at the time of clinical onset of the disease, and that any progression thereafter is slow enough to elude detection during several years of follow-up.