Gradual painless visual loss: chronic optic neuropathies.

The clinician must be the ultimate medical detective when dealing with chronic optic neuropathies. History taking is crucial. Clinical examination may require supplementation with visual field testing, fluorescein angiography, ocular and orbital ultrasound imaging, CT and MR imaging, blood test data, and cerebrospinal fluid or tissue biopsy data to determine the specific diagnosis. This supplementation is labor-intensive and time-consuming; the visual loss usually will progress throughout the process, frustrating and frightening the patient and physician. The final common pathway is gradual optic atrophy; the appearance of the optic nerve is rarely adequate to determine the cause of the visual loss. This article includes tables that review diagnostic aids and therapies, and lists the frequency with which several disease entities were encountered over 15 years in one tertiary care neuro-ophthalmic practice. If a specific cause is discernible, then a specific therapy may be available. This approach has the best chance of saving the patient's vision with the least toxicity caused by erroneous trials. By necessity, the work-up for these patients is expensive, but the cost of not pursuing the cause is irrevocable, permanent blindness.

Comparison of red-green, blue-yellow and achromatic losses in glaucoma.

Achromatic losses in glaucoma would be expected to be greater than, or equal to, red-green chromatic losses if the following assumptions are made: (1) the function of the remaining axons is either unchanged or non-selectively reduced; (2) red-green chromatic information is signaled by the midget ganglion cell system; and (3) the function of the magnocellular system is reduced at least as much as that of the midget ganglion cells. This prediction was tested by measuring red-green (along with blue-yellow) mixture thresholds for 1 deg, 0.2 sec test spots presented on a color monitor on a white background of 50 cd/m2. Ellipses were fitted to plots of green contrast as a function of red contrast (or yellow as a function of blue), and major and minor axes of these ellipses were taken as measures of chromatic and achromatic thresholds, respectively. The study population consisted of 29 eyes in 29 patients with early glaucoma; control data were derived from a data bank of 83 normal eyes. Red-green losses were significantly (P < 0.05) greater than achromatic losses in 6 out of the 11 eyes which showed significant losses of either chromatic or achromatic sensitivity (or both). It is concluded that, for these eyes, at least one of the above three assumptions is incorrect.

Efficient and unbiased modifications of the QUEST threshold method: theory, simulations, experimental evaluation and practical implementation.

QUEST [Watson and Pelli, Perception and Psychophysics, 13, 113-120 (1983)] is an efficient method of measuring thresholds which is based on three steps: (1) Specification of prior knowledge and assumptions, including an initial probability density function (p.d.f.) of threshold (i.e. relative probability of different thresholds in the population). (2) A method for choosing the stimulus intensity of any trial. (3) A method for choosing the final threshold estimate. QUEST introduced a Bayesian framework for combining prior knowledge with the results of previous trials to calculate a current p.d.f.; this is then used to implement Steps 2 and 3. While maintaining this Bayesian approach, this paper evaluates whether modifications of the QUEST method (particularly Step 2, but also Steps 1 and 3) can lead to greater precision and reduced bias. Four variations of the QUEST method (differing in Step 2) were evaluated by computer simulations. In addition to the standard method of setting the stimulus intensity to the mode of the current p.d.f. of threshold, the alternatives of using the mean and the median were evaluated. In the fourth variation--the Minimum Variance Method--the next stimulus intensity is chosen to minimize the expected variance at the end of the next trial. An exact enumeration technique with up to 20 trials was used for both yes-no and two-alternative forced-choice (2AFC) experiments. In all cases, using the mean (here called ZEST) provided better precision than using the median which in turn was better than using the mode. The Minimum Variance Method provided slightly better precision than ZEST. The usual threshold criterion--based on the "ideal sweat factor"--may not provide optimum precision; efficiency can generally be improved by optimizing the threshold criterion. We therefore recommend either using ZEST with the optimum threshold criterion or the more complex Minimum Variance Method. A distinction is made between "measurement bias", which is derived from the mean of repeated threshold estimates for a single real threshold, and "interpretation bias", which is derived from the mean of real thresholds yielding a single threshold estimate. If their assumptions are correct, the current methods have no interpretation bias, but they do have measurement bias. Interpretation bias caused by errors in the assumptions used by ZEST is evaluated. The precisions and merits of yes-no and 2AFC techniques are compared.(ABSTRACT TRUNCATED AT 400 WORDS)

Correlation of chromatic, spatial, and temporal sensitivity in optic nerve disease.

Spearman rank-order correlations (R) were made between the color-mixture threshold, spatial contrast sensitivity, and flicker sensitivity measurements of 38 patients with a variety of optic nerve disorders. Patients had to satisfy the following criteria: greater than 0.5 log unit loss of chromatic or achromatic sensitivity (compared to age-matched normals), central fixation, no congenital color defects, and no ocular media abnormalities. The results of the analysis show a significant correlation between selective losses of high spatial frequency sensitivity (relative to low) and selective losses of red/green and blue/yellow sensitivities [R = -0.680 (P less than 0.001) and R = -0.439 (P less than 0.01), respectively]. A mild correlation was found between selective spatial and selective temporal losses [r = -0.399 (P less than 0.05)] (ie, low temporal frequency losses correlate with high spatial frequency losses and vice versa). A stronger correlation was found between selective red/green and selective blue/yellow sensitivity losses [R = 0.657 (P less than 0.001)]. No correlation was found between selective temporal losses and selective chromatic losses. These findings can be explained in terms of differential losses of three types of fibers: (1) fibers that are particularly sensitive to red/green color, high spatial and low temporal frequencies; (2) fibers signalling blue/yellow color; and (3) fibers that are relatively sensitive to high temporal frequencies and low spatial frequencies.

Upgaze intraocular pressure changes and strabismus in Graves' ophthalmopathy.

Graves' thyroid ophthalmopathy primarily affects women in their third through sixth decade. Sixty-seven patients with clinical myopathic ophthalmic Graves' disease examined (by SCB) between 1982 and 1989 were measured for changes in upgaze intraocular pressure and strabismus. Special attention was paid to "masquerade" symptoms, including pseudosuperior oblique palsies and cyclotorsions. Any correlation between the extent of hypertropia on muscle exam and upgaze intraocular pressure changes is examined. Data suggest that significant changes in introcular pressure in upgaze correlate with more severe extraocular muscle involvement, may represent progression to muscle fibrosis, and occur uniformly in our study of patients who progress to require inferior rectus recession.

Hibiclens keratopathy. A clinicopathologic case report.

A 39-year-old woman developed a painful, red eye immediately following oral surgery associated with preoperative preparation of her face with the antiseptic, Hibiclens. Epithelial and stromal edema was observed 2 weeks after surgery and progressed to diffuse bullous keratopathy. This led to penetrating keratoplasty 10 months later. Light and electron microscopic findings of the cornea included epithelial edema with bullous changes, marked loss of keratocytes, a thickened Descemet's membrane, and an attenuated, disrupted endothelial cell layer. These findings demonstrate the corneal damage that may occur following ocular exposure to Hibiclens.

Chromatic, spatial, and temporal losses of sensitivity in multiple sclerosis.

Chromatic, spatial, and temporal losses of sensitivity were measured in 15 eyes of 10 patients with recovered optic neuritis. Chromatic sensitivities (for both red-green and blue-yellow) were measured using color-mixture thresholds; the chromatic sensitivity loss was classified as "selective" if it was significantly greater than the achromatic loss. Spatial and temporal sensitivities were measured with contrast sensitivity functions and flicker modulation sensitivity, respectively; these losses were classified as selective if the losses at high (spatial or temporal) frequencies were significantly greater (or significantly less) than losses at low frequencies. All patients had central fixation and were optically corrected carefully. In 1 eye, selective losses of sensitivity for red-green and blue-yellow were combined with a selective loss of sensitivity at high spatial (but not temporal) frequencies. This type of loss may indicate a selective loss of small axons in the optic nerve. The 8 other eyes that showed significant losses were generally nonselective in their chromatic, spatial, and temporal losses; this may indicate a nonselective loss of small and large axons.

Incidence and reactivity patterns of skeletal and heart (SH) reactive autoantibodies in the sera of patients with myasthenia gravis.

Serum from patients with myasthenia gravis (MG) contain antibodies to numerous skeletal muscle components in addition to the acetylcholine receptor (AChR). Certain non-AChR skeletal muscle autoantibodies have been shown by absorption to cross-react with cardiac muscle, leading to the designation of 'skeletal and heart' or SH antibodies. This study describes a new procedure for the extraction of human cardiac muscle which allows direct determination of SH antibody reactivity. Serologic evaluation of 17 patients with MG revealed 9/17 (53%) were seropositive for SH antibody to cardiac muscle. Absorption of selected MG serum samples with cardiac muscle extracts, reduced or eliminated reactivity to skeletal muscle in all cases, confirming the presence of cross-reactive antibodies. Immunoblot analysis of cardiac muscle extracts demonstrated several distinct antigenic components, which were unrelated to the acetylcholine receptor or to previously identified striational muscle proteins. Serum samples from individual MG patients displayed different immunoblot reactivity patterns ot the antigens in cardiac muscle extracts, providing the first evidence of multiple heart-reactive SH antibodies in MG.

Corneal edema related to accidental Hibiclens exposure.

Five patients developed corneal edema presumably caused by accidental preoperative ocular exposure to Hibiclens. In all cases, the patients complained of ocular pain after surgery. Conjunctival inflammation and corneal epithelial defects were found in all patients. Between two and ten weeks after exposure, stromal and epithelial edema, with a predilection for the inferior cornea initially, developed in all patients. The corneal edema resolved in three patients in approximately six months, leaving mild stromal scarring and reduced endothelial cell counts. The corneal edema in the other two patients progressed to diffuse bullous keratopathy, which eventually required penetrating keratoplasty. We recommend that Hibiclens be avoided in preoperative preparation of the facial skin to prevent accidental ocular exposure.

Misdiagnosis of iridocyclitis.

Flare cells, and hypotony do not always signify uveitis, but may also be presenting symptoms of a retinal detachment. Unexpected, unusually good intraocular pressure control in a difficult case of glaucoma is less often a cause for rejoicing and more often a result of a retinal detachment.

Posterior decompensation syndrome: macular failure versus senile macular degeneration.

Macular cone death in adults is caused by failure of the system that carries away the retinal biologic wastes. This failure may be termed the posterior decompensation syndrome, a name intended to convey the dynamic concept of imbalance between formation and elimination of waste. Because of centripetal fluid flow in the subretinal space, a disproportionate amount of drusen-like debris accumulates upon the surface of the lamina vitrea at the posterior pole. Recognition of this concept is the key to prevention of macular failure by reducing the amount of waste generated from the peripheral retina or its transport to the macula.

Red-green mixture thresholds in congenital and acquired color defects.

A color television display was used to measure thresholds for mixtures of red and green on a white background; red and green components could be either incremental, decremental or zero. Ellipses are fitted to a plot of green contrast as a function of red contrast, and it is argued that the length of the ellipse is a measure of red-green color discrimination and the width of the ellipse is a measure of luminance discrimination. It is shown that the technique reliably distinguishes normals from congenital color defectives and also protan from deutan subjects. For some cases of acquired color defects (e.g. optic neuritis), there is a roughly equal loss of color and luminance discrimination whereas, in other cases (e.g., hereditary optic atrophies), the loss of color discrimination is much greater than the loss of luminance discrimination.

Color mixture thresholds measured on a color television--a new method for analysis, classification and diagnosis of neuro-ophthalmic disease.

A color television display can be used to determine color and brightness discrimination thresholds using identical adaptation conditions and experimental technique. The color discrimination threshold is measured by using an equiluminous test spot--i.e. one which differs in color from the surrounding screen but has the same luminance. Because there is no brightness clue, the subject is forced to detect such a spot by using color discrimination. It is shown how color and brightness thresholds may be determined from threshold measurements of different color-mixtures even though it is not known beforehand which stimulus will be equiluminous for the subject. Results are shown for normal subjects, congenital color defectives and for two patients having optic nerve disease who show respectively non-selective and selective loss of color discrimination compared to brightness discrimination. Normal control data are presented, illustrating the effect of eccentricity, optical blur, viewing distance, pupil size and age. It is concluded that the technique is relatively insensitive to moderate variations in these factors and that it is more sensitive in detecting selective color loss than a spectral sensitivity technique which has been described previously.

Selective damage to chromatic mechanisms in neuro-ophthalmic diseases I. Review of published evidence.

Acquired color deficiencies may correspond to a general, non-selective loss of visual sensitivity. We summarise evidence for the opposite view that, in some cases, chromatic sensitivity can be more (or less) reduced than achromatic sensitivity. This evidence is based on: (1) Disproportion between chromatic and achromatic isopters; (2) Differential damage to red-green and blue-yellow color vision; (3) Detection static perimetry; (4) The foveal photochromatic interval; (5) The two color threshold technique; (6) Spectral sensitivity on a white background; (7) Single unit and histological studies of the retina and lateral geniculate nucleus; (8) Lesions of the prestriate color area; (9) Selective damage to achromatic processes. Possible problems of interpretation are considered and a new technique for comparing chromatic and achromatic sensitivity is briefly described.

A study of volunteer ambulance squads.

A study of all 37 ambulance squads in two Pennsylvania counties (Lehigh and Northampton), an area known to be served largely by volunteer units, was carried out by personal on-site interviews in 1973. The objectives were to determine the structure and functions of the squads and to devise some preliminary estimates of effectiveness as a base for regional planning. Topics examined include population and geographic area served, numbers and training of personnel, vehicles, equipment, record keeping, finances, communications capabilities, and squad organization. The 34 volunteer squads were found to vary greatly in resources and sophistication. The rural squads in particular tended to be underfinanced, to have low call loads and a delayed response to calls. In some squads personnel were inadequate in numbers and training. The advantages and disadvantages of maintaining volunteer services in rural areas are discussed and some possible approaches to the problem of providing high-quality services in rural areas outlined.