A 70-year-old woman was seen in neuro-ophthalmology consultation for a progressive right esotropia. She had a past medical history of asthma and osteoporosis, and her ocular history was significant for pathological myopia (spherical equivalent of −23.00 D OD and −21.00 D OS), bilateral cataract surgeries, and laser retinopexy for retinal tears. Twenty-five years prior to presentation, she developed binocular horizontal diplopia and was found to have a limitation of abduction to 60% and 80% of normal in the right and left eyes, respectively, by a previous neuro-ophthalmologist. She developed a progressive maculopathy in the right eye secondary to myopia, resulting in the resolution of double vision. The resolution occurred because the double vision was binocular in nature and the loss of vision in her right eye functioned similar to monocular occlusion. However, she noticed that her right eye continued to turn in toward her nose.

Recent work has implicated one type of horizontal strabismus (exotropia) as a risk factor for schizophrenia. This new insight raises questions about a potential common developmental origin of the two diseases. Seasonality of births is well established for schizophrenia. Seasonal factors such as light exposure affect eye growth and can cause vision abnormalities, but little is known about seasonality of births in strabismus. We examined birth seasonality in people with horizontal strabismus in a retrospective study in Washoe County, Nevada, and re-examined similar previously obtained data from Osaka, Japan. We then compared seasonal patterns of births between strabismus, refractive error, schizophrenia and congenital toxoplasmosis. Patients with esotropia had a significant seasonality of births, with a deficit in March, then increasing to an excess in September, while patients with exotropia had a distinctly different pattern, with an excess of births in July, gradually decreasing to a deficit in November. These seasonalities were statistically significant with either χ2 or Kolmogorov–Smirnov-type statistics. The birth seasonality of esotropia resembled that for hyperopia, with an increase in amplitude, while the seasonality for myopia involved a phase-shift. There was no correlation between seasonality of births between strabismus and congenital toxoplasmosis. The pattern of an excess of summer births for people with exotropia was remarkably similar to the well-established birth seasonality of one schizophrenia subtype, the deficit syndrome, but not schizophrenia as a whole. This suggests a testable hypothesis: that exotropia may be a risk factor primarily for the deficit type of schizophrenia.

Amblyopia is a developmental disorder that affects the spatial vision of one or both eyes in the absence of an obvious organic cause; it is associated with a history of abnormal visual experience during childhood. Subtypes have been defined based on the purported etiology, namely, strabismus (misaligned eyes) and/or anisometropia (unequal refractive error). Here we consider the usefulness of these subclassifications.

Strabismus represents a complex oculomotor disorder characterized by the deviation of one or both eyes and poor vision. A more sophisticated understanding of the genetic liability of strabismus is required to guide searches for associated molecular variants. In this classical twin study of 1,462 twin pairs, we examined the relative influence of genes and environment in comitant strabismus, and the degree to which these influences can be explained by factors in common with refractive error. Participants were examined for the presence of latent (‘phoria’) and manifest (‘tropia’) strabismus using cover–uncover and alternate cover tests. Two phenotypes were distinguished: eso-deviation (esophoria and esotropia) and exo-deviation (exophoria and exotropia). Structural equation modeling was subsequently employed to partition the observed phenotypic variation in the twin data into specific variance components. The prevalence of eso-deviation and exo-deviation was 8.6% and 20.7%, respectively. For eso-deviation, the polychoric correlation was significantly greater in monozygotic (MZ) (r = 0.65) compared to dizygotic (DZ) twin pairs (r = 0.33), suggesting a genetic role (p = .003). There was no significant difference in polychoric correlation between MZ (r = 0.55) and DZ twin pairs (r = 0.53) for exo-deviation (p = .86), implying that genetic factors do not play a significant role in the etiology of exo-deviation. The heritability of an eso-deviation was 0.64 (95% CI 0.50–0.75). The additive genetic correlation for eso-deviation and refractive error was 0.13 and the bivariate heritability (i.e., shared variance) was less than 1%, suggesting negligible shared genetic effect. This study documents a substantial heritability of 64% for eso-deviation, yet no corresponding heritability for exo-deviation, suggesting that the genetic contribution to strabismus may be specific to eso-deviation. Future studies are now needed to identify the genes associated with eso-deviation and unravel their mechanisms of action.

Previous experiments in animals have shown that early unilateral eyelid suture, a model of amblyopia induced by cataract, causes shrinkage of ocular dominance columns serving the deprived eye in the striate cortex. It is unknown whether the ocular dominance columns are affected in amblyopia produced by strabismus. We examined specimens of striate cortex obtained postmortem from a 79-year-old woman with a history of amblyopia in her left eye (20/800) since age 2 from accommodative esotropia. Four years prior to her death, she suffered an ischemic infarct of the left optic disc. This injury to the left optic disc made it possible to label the ocular dominance columns using cytochrome oxidase histochemistry. The pattern of ocular dominance columns was reconstructed throughout most of the right striate cortex. No shrinkage of columns was found. In the left cortex only half the column mosaic was labelled, because the patient had some residual vision in the temporal retina of her left eye. The columns within the labelled portion of the overall mosaic appeared normal. These findings indicate that shrinkage of ocular dominance columns does not occur in humans with amblyopia caused by accommodative esotropia. The ocular dominance columns are probably no longer susceptible to shrinkage at the age when most children with this condition begin to develop amblyopia.

The effect of experimental strabismus on the development of vernier acuity and grating acuity was studied in Macaca nemestrina monkeys. Six monkeys were studied longitudinally beginning near 10 days after birth. Four of the six monkeys developed amblyopia. As is true for human strabismic amblyopes, the deficit in vernier acuity was larger than the deficit in grating acuity in the amblyopic monkeys. The developmental data reveal that this differential disruption of vernier acuity can be understood as a result of a slowed developmental process associated with amblyopia.

We have examined the effects of rearing kittens with a unilateral convergent strabismus, induced surgically at 3 weeks of age, on the binocularity (ocular dominance) and receptive-field position of neurons in the motion-sensitive lateral suprasylvian (LS) area of cat extrastriate cortex. Data were compared to those obtained from area 17 in the same animals, and from the two areas of cortex in normal adult cats. Interocular alignment of the operated cats was assessed in alert adults using corneal reflex photography and during recording from the positions of retinal landmarks under paralysis. The strabismus magnitude in each operated cat was calculated by comparison with equivalent data from the normal animals.

Strabismus always caused a major loss of binocularity in area 17. The remaining binocular neurons had receptive-field (RF) pairs arising from positions of normal correspondence in the two retinae and would thus have been responsive to different regions of visual space through the misaligned eyes in the alert animal. In area LS, the effects were dependent on the strabismus magnitude. In the group of four cats with pronounced strabismus (18–30 deg crossed), a loss of binocularity occurred in area LS equivalent in severity to that in area 17. The majority of the remaining binocular LS neurons possessed RF pairs in normal retinal correspondence and would thus, in the alert animal, have received spatially disparate visual input through the two eyes. This also occurred in three other cats with more moderate strabismus (11–15 deg crossed), although only a small breakdown in the binocularity of area LS was apparent. The group of cats with mild strabismus (≤10 deg crossed) had normal proportions of binocular neurons in area LS. In three of these cats, the maintenance of binocularity was accompanied by shifts in RF position, with visual inputs arising from anomalous retinal locations. These shifts compensated, in part, for the strabismus angle present in each cat, so that most of the binocular LS neurons would have received inputs from regions of visual correspondence through the misaligned eyes when the animal was alert.

Similar mechanisms could afford a basis for the binocular visual compensations that occur in humans with small-angle strabismus of early onset. If so, anomalous retinal correspondence in such individuals would have as a locus areas of extrastriate cortex with a role in motion perception, and would involve alterations to the neural substrate underlying normal binocular vision.

The anatomical substrate of the pupillary light reflex was investigated in normal and innate microstrabismic cats using anatomical methods as well as electrical stimulation. The bilateral retinal input to the nucleus praetectalis olivaris (NPO), the pretectal relay station in the subcortical pupilloconstrictor pathway, was identified to come from the ventral retina where the upper visual field is represented. Orthodromic electrical stimulation revealed that retinal information is transmitted to on-tonic neurons in the NPO mainly via slowly conducting axons probably originating from W- and X-type retinal ganglion cells.

For the first time, a direct cortical input to on-tonic neurons in the NPO could be demonstrated. This cortical input originates from caudolateral parts of the occipital cortex. Putative input structures are those subdivisions of areas 19 and 20a where the upper part of the visual field is represented.

A direct, predominantly contralateral projection with a weak ipsilateral component from NPO to the nucleus of Edinger-Westphal, and an interhemispheric connection between the NPOs could be demonstrated. With respect to the anatomical connections as described in this study, no differences between normal and innate microstrabismic cats could be found.

The results are discussed with respect to the binocular summation of the pupillary light reflex and its reduction in subjects with impaired binocular vision.

It has been suggested that development of central connections in the mammalian visual system is governed by a simple Hebbian rule of synaptic modifiability. Under such a rule, simultaneity of presynaptic and postsynaptic action potentials is a prerequisite for enhanced synaptic efficacy. The present paper reports the results of a study designed to test whether this hypothesis is applicable to the development of the thalamo-cortical visual pathway.

In four-week-old kittens, exposure to a 2-d period of monocular deprivation was used to render the vast majority of cortical cells capable of being activated only by the nondeprived eye. During a subsequent 3–5 month recovery period, both eyes were open but surgically misaligned. This combination of conditions was chosen so that during the recovery period presynaptic activity originating from the initially deprived eye would be decorrelated from postsynaptic action potentials in cortical neurons. If synaptic modification is regulated by a simple Hebbian mechanism, then in this situation the deprived eye should be unable to recover control of cortical cells.

In fact, the present results indicate that during the recovery period the proportion of cortical neurons dominated by the deprived eye rose to a level equal to that of the nondeprived eye – a result contrary to that predicted by a simple Hebbian rule of development. Histological analysis indicated that a similar level of recovery was present both within and outside of cortical layer IV, the main thalamo-recipient layer. As expected, the induced strabismus resulted in a failure of cortical binocularity to recover in these kittens.

Although these results argue against a simple Hebbian mechanism of development, they are compatible with the hypothesis that synaptic modifiability is dependent upon correlations between presynaptic activity and local, subthreshold, postsynaptic changes. This alternative hypothesis has the advantage of allowing modification of local synaptic circuits within the dendritic arbors of a single neuron.

The eyes of adult barn owls (Tyto alba) are virtually fixed in the head in positions that are highly consistent from one individual to the next. However, early in development the eyes are exodeviated; the eyes achieve their adult positions during the owl's second month of life. Disruption of binocular vision in baby owls leads to permanent, highly abnormal eye positions and interocular alignment. Of three owls raised with both eyelids sutured closed, two developed exotropic strabismus and one developed esotropic strabismus. Two owls reared with monocular vision developed esotropic strabismus, whereas three owls reared with fused, but optically deviated binocular vision developed normal eye positions. Thus, the alignment of the eyes in adults results from an active process that depends on fused binocular vision during early life.

Extracellular microelectrode recordings from the optic tecta of strabismic owls reveal that many units retain binocular inputs from corresponding points of the two eyes: the left-eye and right-eye receptive fields of individual units are misaligned by an amount predicted by the direction and magnitude of the strabismus. These results indicate that an innately determined pattern of connections in the brain anticipates the eye positions necessary to achieve binocular fusion. The hypothesis is put forth that the powerful activation of such binocular neurons by strong, synchronous inputs from the two eyes is the signal required by the optimotor system that proper eye alignment has been attained.

Strabismus induces an abnormal pattern of alternating light and dark columns of cytochrome oxidase (CO) activity in macaque striate cortex. This pattern may arise because visual perception is suppressed in one eye to avoid diplopia. To test whether CO activity is reduced in the ocular dominance columns of the suppressed eye, we performed monocular enucleation to co-label the ocular dominance columns with Zif268 immunohistochemistry in seven exotropic adult Macaca fascicularis. This approach was unsuccessful, for two reasons. First, Zif268 yielded inconsistent labelling, that was usually greater in the enucleated eye's ocular dominance columns, but was sometimes greater in the intact eye's columns. Therefore, Zif268 was not a reliable method for identifying the ocular dominance columns serving each eye. Second, in three control animals we found that a brief survival period following monocular enucleation (needed for Zif268 levels to change) was long enough to alter CO staining. For example, a survival time of only 3 h was sufficient to induce CO columns, indicating that the activity of this enzyme fluctuates more rapidly than realized previously. Independent of these findings, we have also discovered that acute monocular enucleation produces a vivid pattern of ocular dominance columns visible in unstained or CO-stained sections under dark-field illumination. The ocular dominance columns of the acutely enucleated eye appear dark. This was verified by labelling the ocular dominance columns with [3H]proline. Dark-field illumination of the cortex after acute monocular enucleation offers a new, easy method for identifying the ocular dominance columns in macaques.

This prospective, randomized and double-blinded study was designed to evaluate the anti-emetic efficacy of a combination of ondansetron and metoclopramide in 100 ASA physical status I and II children of either sex and 1–15 years of age undergoing elective surgery for strabismus. A standardized anaesthetic technique and post-operative analgesia were used for all the children. Children were divided into four groups. They received saline, metoclopromide 250 μg kg−1, ondansetron 150 μg kg−1 or a combination of metoclopramide 150 μg kg−1 and ondansetron 100 μg kg−1 intravenously immediately after the insertion of an intravenous cannulae. There were no differences between the groups in their age, gender, weight, duration of surgery, number of muscles subjected to surgery or intravenous fluids received. In the first 24 post-operative hours, 18 (72%) patients in the placebo group, 15 (60%) patients in the metoclopramide group, 10 (40%) patients in the ondansetron group and 11 (44%) patients in the combination group had nausea or vomiting. The overall incidence of post-operative nausea and vomiting was significantly (P<0.05) lower in the combination group and in the ondansetron group compared with the placebo group. Nine (36%) patients in both the placebo and the metoclopramide groups and one (4%) patient in the ondansetron group required rescue anti-emetic treatment. None of the patients in the combination group required rescue anti-emetic and this was significantly less (P <0.01) when compared with the placebo and the metoclopramide groups. Recovery and sedation scores were comparable in all the four groups. A combination of metoclopramide 150 μg kg−1 and ondansetron 100 μg kg−1 administered prior to surgery was not found to be more effective than ondansetron 150 μg kg−1 alone for the prophylaxis of nausea and vomiting following surgical repair of strabismus in paediatric patients.

Record linkage of the Finnish Twin Cohort Study with the Hospital Discharge Registry and with the Registry of Rights to Free Medication kept by the Social Insurance Institution gave following numbers of twin pairs with an ophthalmic disease (one or both members of the pair had the disease) in each disease category:98 with glaucoma simplex (5 concordant pairs), 38 with capsular glaucoma (no concordant pairs), 58 with iritis (no concordant pairs) and 149 with strabismus (2 concordant pairs).

The number of concordant pairs in each disease category was small, except for glaucoma simplex in which concordant pairs could be broken down by zygosity. The ratio of observed to expected (based on association by chance) was 6.96 for MZ and 1.74 for DZ pairs. This result suggests that genetic factors play some role in the variability of prevalence of simple glaucoma. Main etiologic factors are stili to be found in the environment. Data on occurrence of other diseases of ophtalmologic importance is presented.