Physiological basis of anisometropic amblyopia.

In the visual cortex of kittens that have received their only visual experience while wearing a high-power lens before one eye, most neurons are dominated by input from the normal eye. Moreover, contrast sensitivity and resolving power are lower for stimulation through the originally defocused eye, mimicking psychophysical results from human anisometropic amblyopes.

Natural strabismus in monkeys. Convergence errors assessed by cover test and photographic methods.

A standard set of clinical prism and cover tests and a recently developed photographic method were used to assess binocular alignment in ten monkeys that previously were determined to have a naturally occurring infantile strabismus. Extensive measurements of the alignment state were made for fixation attempts throughout the field of gaze. Patterns of alignment errors were examined in an attempt to compared the strabismus found in individual monkeys with common syndromes of human infantile strabismus. Two monkeys showed patterns consistent with the syndrome of essential infantile esotropia. Five monkeys had patterns consistent with accommodative esotropia. One monkey that had bilateral anterior chamber hemorrhage at birth had a constant-angle esotropia. One monkey that previously had been shown to have a large-angle esotropia during development exhibited only exophoria, and in a final monkey in which large-angle esotropia was found during development, the strabismus had resolved. These results demonstrate that naturally occurring strabismus in monkeys might be related to syndromes seen in children. In addition, they provide extensive information about other characteristics of strabismus that have not been examined previously. These include a characterization of the magnitude of the misalignment in terms of error surface plots of bias and a detailed analysis of scatter in the measurements that show coupling relationships between the two eyes.

Postnatal axial eye elongation in normal and visually deprived rhesus monkeys.

The influence of anomalous visual experience on the postnatal regulation of axial eye elongation was explored by raising newborn rhesus monkeys under different types of monocular and binocular deprivation and comparing their eye growth pattern with that of age-matched normal monkeys. Monocular manipulations included eyelid suture to eliminate pattern vision; continuous occlusion with an opaque lens to prevent visual experience; surgical removal of the natural lens to induce continuous blur; and correction of surgically induced aphakia with extended-wear contact lenses (EWCLs) to provide a focused image of near objects. Binocular manipulations involved correction of aphakia with an EWCL in one eye and continuous or partial occlusion of the phakic fellow eye. After monocular eyelid suture or occlusion, the deprived eyes were longer than the unmanipulated fellow eyes. Aphakic eyes, however, were shorter than their unmanipulated fellow eyes. The unmanipulated eyes followed the eye elongation pattern of age-matched normal monkeys. Binocular manipulations also resulted in differences in axial length between the two eyes. Aphakic eyes were shorter, and continuously occluded eyes were longer, than eyes of age-matched controls. After partial occlusion, however, the axial length of occluded eyes was similar to that of normal eyes. The finding that lid-sutured and occluded eyes become longer while aphakic eyes remain shorter than normal eyes suggests that additional factors besides retinal image quality control postnatal eye growth.

Cone dystrophy, nyctalopia, and supernormal rod responses. A new retinal degeneration.

An unusual retinal degeneration considered to be inherited as an autosomal recessive trait occurred in two of four children in a Hispanic family. The abnormality causes a progressive and generalized loss of cone vision, including decreased acuity, decreased color vision, central scotomas to small test objects, photo-phobia, and a profound diminution of the cone-mediated electroretinographic (ERG) pattern. A loss of the foveal reflex and an increased granularity of the macula is seen funduscopically. In addition, there is a most unusual alteration of the rod system detectable in the rod-mediated ERG pattern. This rod response is supernormal in amplitude (greater than 1,000 microV, extrapolated), delayed in time course, and insensitive to dim stimuli, ie, the function relating response to light intensity has been drastically altered. The insensitivity to dim stimuli is accompanied by a mild nyctalopia. Some of these abnormalities could be caused by a defect in the retinal enzyme, cyclic nucleotide phosphodiesterase.

Congenital ocular motor apraxia and brainstem tumor.

Congenital ocular motor apraxia is considered a benign disorder of horizontal saccadic eye movements. A case is presented of an 8-month-old boy with this clinical picture in whom, four months later, signs of increased intracranial pressure from a large, cystic neoplasm of the rostral part of the brainstem developed, the second such case reported to our knowledge. Occasional abnormalities of the nervous system in patients with this disorder are reviewed. Careful neurologic examination and continuing reevaluation of the conditions of these patients are encouraged, with consideration of computerized axial tomography of the brain if neurologic findings or deterioration dictates.

Acquired optociliary shunt vessels in papilloedema.

Seven cases are presented in which prolonged papilloedema led to the development of acquired optociliary shunt vessels. These vessels may also be found with optic nerve tumours, particularly spheno-orbital meningiomas, optic nerve drusen, glaucoma, and after central retinal vein occlusion. Two patients had intracranial tumours, 4 benign intracranial hypertension, and one Crouzon's disease. Three had marked atrophic changes of the disc. The pathophysiology of the disc changes is discussed. The triad of long-standing poor vision, acquired optociliary shunts, and optic atrophy with blurred disc margins should not be regarded as specific for spheno-orbital meningioma.

Current state of therapy for amblyopia.

The effectiveness of minimal occlusion therapy and the CAM vision stimulator are discussed as well as optical correction of neonatal aphakia. Results of several early studies and work in progress are given.

Enzyme immunoassay with flow-amperometric detection of NADH.

Using phenytoin as a model analyte, we demonstrate that an enzyme-coupled immunoassay based on flow-injection analysis and amperometric detection of NADH is both feasible and practical. Good agreement with a routine clinical laboratory procedure for phenytoin was obtained for patients' serum samples. The electrode must be protected to prevent fouling by proteins in the analytical sample. The optimum detection range for NADH was at 0.01 of the concentrations of NADH generated during the several minutes required for each analysis. This suggests that the electrochemical technique should be extendable to the determination of species at concentrations in the microgram per liter range.

Effects of early unilateral blur on the macaque's visual system. I. Behavioral observations.

We raised 8 macaque monkeys with chronic atropinization of one eye throughout the first 6-10 months after birth. This rearing procedure produces retinal image blur, with the most pronounced contrast attenuation occurring at high spatial frequencies. Measurements of contrast sensitivity were made using behavioral methods in 6 monkeys and evoked potential methods in 2 monkeys. The results showed that this rearing procedure produced long-term deficits in the contrast sensitivity and spatial resolution of the atropinized eye, which were not due to residual losses in accommodative capacity. There was considerable interanimal variation in the magnitude of the effects on visual performance. Similar losses in visual performance are seen in some forms of human amblyopia. Rearing monkeys with chronic instillation of atropine therefore provides a nonhuman primate model for studying the underlying neural mechanisms of anisometropic amblyopia.

Effects of early unilateral blur on the macaque's visual system. III. Physiological observations.

We studied the properties of visual cortical and lateral geniculate neurons in 5 macaque monkeys raised with the vision of one eye blurred by daily instillation of atropine. This rearing reduced the degree of binocular interaction in striate cortical neurons and caused a modest shift in eye dominance away from the atropine-treated eye. It also led to a difference in the spatial properties of neurons driven by the 2 eyes: neurons driven by the treated eye tended to have lower optimal spatial frequencies, poorer spatial resolution, and lower contrast sensitivity than neurons driven by the untreated eye. Some of the few binocularly driven neurons had receptive fields with sharply different spatial properties in the 2 eyes, with the treated eye's receptive field always having poorer spatial resolution. In striate cortex, the effects on neuronal spatial properties were less marked in layer 4 than in more superficial or deeper layers; there was no difference in the spatial properties of lateral geniculate neurons driven by the 2 eyes. A small sample of extrastriate cortical neurons from a single animal showed effects similar to those seen in striate cortex. The striate cortical changes varied consistently from animal to animal: The less affected animals had no discernible eye dominance shift and relatively small differences in spatial properties between the eyes; the more affected animals had substantial eye dominance shifts and larger interocular spatial differences. These variations were also reflected in, and consistent with, behavioral and anatomical measurements performed in the same monkeys.

Effects of early unilateral blur on the macaque's visual system. II. Anatomical observations.

We studied the effects of early unilateral blur on the anatomical organization of the visual pathways in 8 macaque monkeys. Blur was induced in one eye, beginning 2-14 d after birth, by 0.5% atropine twice a day. Atropinization was stopped at 6-8 months of age, and the animals were studied for anatomy 3-24 months later. The retina and all other eye tissues showed normal histology. In the dorsal lateral geniculate nucleus (LGN), cells in parvocellular layers receiving input from the atropine-treated eye were 9-32% smaller and were more lightly stained than those in layers innervated by the untreated eye. These changes were generally larger in the LGN ipsilateral to the treated eye. LGN cell size changes were absent or much smaller in the magnocellular layers. In the striate cortex, the distribution of the oxidative enzyme cytochrome oxidase (CO) was markedly altered in layer 4C beta. Layer 4C beta is uniformly stained in normal animals, but showed a distinct pattern of alternating high and low CO bands in the atropine-treated animals; the bands of higher CO activity were narrower than the bands of lower activity and had a 857-1050 micron repeat. Fainter banding was seen in layers 4A, 4C alpha, and 6, but the density of the rows of dark CO-stained dots in layer 3 was unaffected. Double-labeling revealed that the narrow dark CO bands were associated with the centers of the ocular dominance columns devoted to the atropine-treated eye. The distribution of 14C-2-deoxyglucose uptake in visual cortex produced by 4.5-9 c/deg spatial frequency stimulation was strongly biased toward the untreated eye. The treated eye could, however, elicit reasonably strong uptake when stimulated with patterns containing lower spatial frequencies. These results suggest that unilateral neonatal blur preferentially affects the parvocellular layers of the LGN and layer 4C beta of striate cortex, which are the portions of the central visual system associated with the processing of information concerning fine spatial detail. These anatomical changes are consistent with the high spatial frequency loss of vision demonstrated behaviorally and electrophysiologically in the atropine eye-driven visual system of these same animals.