Normal and abnormal space perception.

To compare the macular and nerve fiber layer thicknesses as measured by optical coherence tomography (OCT) in amblyopic and fellow eyes. Fifty patients with monocular strabismic (n = 25) or anisometropic (n = 25) amblyopia (best corrected visual acuity (BCVA) ranging from 20/40 to 20/400) were included in a prospective cross-sectional descriptive study. A refractive error more than 5 diopters in either eye or an axial length difference between the eyes of more than 1 mm was excluded in the anisometropic group. In all cases, the thickness of the macular area and the peripapillary nerve fiber layer were measured by OCT in both amblyopic and fellow eyes and compared with each other. The mean age of patients was 10 ± 3.1 years (range: 6 to 18 years) in the anisometropic group and 8.9 ± 3.7 years (range: 6 to 18 years) in the strabismic group. In the anisometropic group, the mean macular thickness was significantly increased in the amblyopic eyes (222.6 ± 47.8 μm) versus the fellow eyes (205.6 ± 33.3 μm) (P = .002), although there was no significant difference observed when comparing with the prepapillary nerve fiber layer (P = .55). There was no significant correlation of above-mentioned matters in the strabismic group (P = .07 and .52). A thicker macula was found in anisometropic amblyopic eyes, but the increase of macular thickness in strabismic amblyopic eyes was not significant. Retinal involvement was not observed in the peripapillary nerve fiber layer of amblyopic eyes.

BackgroundThe aim of this study was to examine the relationship or differences in ocular structures of amblyopic eyes compared to fellow eyes in children and young adults with hyperopic anisometropic amblyopia.Material/MethodsHyperopic participants with anisometropic amblyopia, defined as the presence of best-corrected visual acuity differences of at least 2 Snellen lines and 1.5 diopters between amblyopic and fellow eyes, were studied. Using the IOL Master, Pentacam Scheimpflug imaging and Spectralis optical coherence tomography, the axial length, corneal curvature, and anterior chamber depth (ACD), as well as the thickness of the cornea, peripapillary retinal nerve fiber layer (RNFL), and macula, were compared between children and young adults and between their amblyopic and fellow eyes.ResultsIn 53 participants with hyperopic anisometropic amblyopia, there were significant differences in the anterior corneal curvature, ACD and axial length between the amblyopic and fellow eyes of all the patients. The mean central macular thickness in the amblyopic eyes was significantly thicker (P=.001) in the group aged 5 to 12 years; however, this was not the case in the group aged 13 to 42 years. There was no significant difference in average RNFL thickness in either group.ConclusionsWe found significantly greater mean central macular thickness in anisometropic amblyopic eyes among participants aged 5 to 12 years, but not among those who were older. Similarly, the interocular differences in axial length parameters seemed to be related to the central macular thickness differences between the amblyopic and fellow eyes in the younger group.

The preferred eyes of strabismic amblyopes, generally presumed to be normal, have been implicated by recent studies as manifesting oculomotor abnormalities. We sought to determine whether these motor abnormalities occurred together and, if so, whether they could be related to a single underlying deficit. Occurring together in the preferred eyes of our strabismic amblyopes were: unsteady fixation (consisting of nasal drifts alternating with temporal saccades), minute fixational eccentricity (as indicated by eccentric directionalization of the Maxwell spot) and asymmetries of pursuit tracking. These motor abnormalities of the preferred eye are attributable to the presence of high-velocity nasal drifts. Since nasal drifts also account for several qualitatively similar motor abnormalities exhibited under monocular conditions by the fellow amblyopic eye, we conclude that a centrally-generated nasal drift bias is responsible for anomalous oculomotor behaviors of both eyes of strabismic amblyopes.

The present study aimed to explore temporal frequency discrimination in amblyopia, and the influence of attentional load on amblyopic temporal cognition. Twenty anisometropic amblyopes, 20 strabismic amblyopes and 20 normal subjects were recruited. A flickering disk was used for visual stimuli. A two-alternative, forced-choice staircase paradigm was used to measure the temporal frequency discrimination thresholds of amblyopic eyes, fellow eyes and normal dominant eyes under reference temporal frequencies of 5, 10 and 20 Hz. The just-noticeable differences data were analyzed statistically. In addition, the temporal frequency discrimination thresholds of the subjects were measured under different conditions of attentional load. The changes in temporal frequency discrimination thresholds were compared between amblyopic and normal eyes when attention was loaded. At the reference temporal frequencies of 5 and 10 Hz, temporal thresholds of amblyopic eyes were significantly increased compared with fellow eyes (P<0.05). Regarding strabismic amblyopia, temporal thresholds of fellow eyes were increased compared with normal eyes (P<0.05). However, no correlation was identified between the temporal-frequency discrimination thresholds and the LogMAR visual acuities in amblyopic eyes. In addition, higher attentional load caused greater changes in temporal thresholds in amblyopic eyes, but the situation was not the same for lower attentional load. In conclusion, in the present study a deficit of temporal frequency discrimination in amblyopic eyes and the fellow eyes of strabismic amblyopes was identified. Furthermore, the influence of attentional load on temporal frequency discrimination in amblyopic eyes was increased compared with normal eyes.

In amblyopia, abnormal visual experience leads to an extreme form of eye dominance, in which vision through the nondominant eye is degraded. A key aspect of this disorder is perceptual suppression: the image seen by the stronger eye often dominates during binocular viewing, blocking the image of the weaker eye from reaching awareness. Interocular suppression is the focus of ongoing work aimed at understanding and treating amblyopia, yet its physiological basis remains unknown. We measured binocular interactions in visual cortex of anesthetized amblyopic monkeys (female Macaca nemestrina), using 96-channel "Utah" arrays to record from populations of neurons in V1 and V2. In an experiment reported recently (Hallum et al., 2017), we found that reduced excitatory input from the amblyopic eye (AE) revealed a form of balanced binocular suppression that is unaltered in amblyopia. Here, we report on the modulation of the gain of excitatory signals from the AE by signals from its dominant fellow eye (FE). Using a dichoptic masking technique, we found that AE responses to grating stimuli were attenuated by the presentation of a noise mask to the FE, as in a normal control animal. Responses to FE stimuli, by contrast, could not be masked from the AE. We conclude that a weakened ability of the amblyopic eye to modulate cortical response gain creates an imbalance of suppression that favors the dominant eye.SIGNIFICANCE STATEMENT In amblyopia, vision in one eye is impaired as a result of abnormal early visual experience. Behavioral observations in humans with amblyopia suggest that much of their visual loss is due to active suppression of their amblyopic eye. Here we describe experiments in which we studied binocular interactions in macaques with experimentally induced amblyopia. In normal monkeys, the gain of neuronal response to stimulation of one eye is modulated by contrast in the other eye, but in monkeys with amblyopia the balance of gain modulation is altered so that the weaker, amblyopic eye has little effect while the stronger fellow eye has a strong effect. This asymmetric suppression may be a key component of the perceptual losses in amblyopia.

PurposeTo determine the differences and reproducibility of blood flow among hyperopic anisometropic, fellow, and control eyes.MethodsWe retrospectively studied 38 eyes of 19 patients with hyperopic anisometropia (8.2 ± 3.0 years of age) and 13 eyes of eight control patients (6.8 ± 1.9 years). We measured the optic nerve head (ONH) and choroidal circulation using laser speckle flowgraphy (LSFG) and analyzed the choroidal mean blur rate (MBR-choroid), MBR-A (mean of all values in ONH), MBR-V (vessel mean), MBR-T (tissue mean), and sample size (sample), which are thought to reflect the ONH area ratio, area ratio of the blood stream (ARBS). We then assessed the coefficient of variation (COV) and intraclass correlation coefficient (ICC) and compared the differences among amblyopic, fellow, and control eyes in MBR, sample, and ARBS.ResultsThe ONH, MBR-A, MBR-T, and ARBS of amblyopic eyes were significantly higher than those of fellow eyes (P < 0.01, P < 0.05, and P < 0.05, respectively), and control eyes (MBR-A and ARBS, P < 0.05, for both comparisons). The sample-T (size of tissue component) in amblyopic eyes was significantly smaller than that in fellow and control eyes (P < 0.05). Blood flow in the choroid did not differ significantly between the eyes. The COVs of the MBR, sample, and ARBS were all ≤10%. All ICCs were ≥0.7. The COVs of pulse waveform parameter fluctuation, blowout score (BOS), blowout time (BOT), and resistivity index (RI) in the ONH and choroid were ≤10%.ConclusionThe MBR value of the LSFG in children exhibited reproducibility. Thus, this method can be used in clinical studies. The MBR values of the ONH in amblyopic eyes were significantly high. It has been suggested that measuring ONH blood flow using LSFG could detect the anisometropic amblyopic eyes.

The aim of this study was to investigate the spatial and temporal distortions that occur in strabismic and anisometropic amblyopic vision. Twelve subjects with strabismic (n = 4), anisometropic (n = 4), mixed amblyopia (n = 3) and bilateral refractive amblyopia (n = 1) were asked to describe and sketch their subjective percept of different geometrical patterns, as seen with their amblyopic eye. Based on their descriptions, computer-animated patterns were generated, which were then validated by the subjects. Both spatial distortions and temporal instability were perceived mainly by strabismic and strabismic-anisometropic amblyopes. Temporal instability occurred mainly at high spatial frequencies. Our data suggest that strabismus, in addition to amblyopia, is needed to elicit significant spatial and temporal distortions. The occurrence of these distortions may be related to the early history of each subject.

The other side of amblyopia

Objective: To detect the pathogenetic mechanism of motion-sensitive cortical deficit in response to motion stimuli in children with anisometropic amblyopia using a blood oxygenation level-dependent functional magnetic resonance imaging technique (BOLD-fMRI). Methods: This was a case series study. Patients were collected from June to December 2017 at Tianjin Eye Hospital. Twenty-five patients who were diagnosed with anisometropic amblyopia as amblyopia group and twenty-five normal volunteers were examined as control group. A BOLD-fMRI technique on a 1.5T MRI and a horizontally moving sinusoidal grating block design were used for task conditions. All data were processed with SPM5 software, were analyzed by t test. Results: Significant fMRI activation and comparable right and left eye activation were found in the middle temporal area (MT), and Brodmann areas 19 and 37, in all control subjects; Lesser cortical activation in area MT and Brodmann areas 37, 19, and greater activation in the frontal gyrus of the lazy eye group were detected compared to the control group. Lesser cortical activation in Brodmann area 37, 18 of the contralateral eye of the amblyopic group was detected compared to the control group. Lesser cortical activation in area MT and Brodmann areas 19, 18, and greater activation in the frontal lobes of the anisometropic amblyopic eyes were detected compared to the contralateral eyes. Conclusions: The spatial extent and intensity of the visual cortex activation in the visual cortex decreases in the amblyopic eye compared to the normal control. Decreased cortical activation in the fellow eye is prevalent. A greater visual cortex area is activated when stimulating the amblyopic eye. Key words: Anisometropia; amblyopia; magnetic resonance imaging; visual motion; cortical deficit

To determine the impact of wearing single-vision spectacle lenses (SVLs) on the refractive errors at the periphery of the retina in myopic eyes of Chinese children. Twenty-eight children (8 to 15 years) were divided into two groups: one (n = 17) comprising children with low myopia (spherical equivalent between -0.75 D and -3.00 D inclusive) and the other (n = 11), with moderate myopia (spherical equivalent between -3.25 D and -6.00 D inclusive). Cycloplegic autorefraction from right eyes was measured at the fovea and at 20, 30, and 40 degrees in the temporal and nasal visual fields. Measurements were taken on each subject both while uncorrected and while wearing SVLs. Hyperopic peripheral defocus was found with SVLs in both the low and moderate myopia groups. However, the increase in relative peripheral hyperopic defocus when wearing spectacle correction, when compared with the uncorrected state was statistically significant for the moderate myopia group only. In the moderate myopia group, relative peripheral hyperopic defocus when wearing spectacle correction was statistically significantly greater vs. the low myopia group at 40 degrees in the nasal field and at both 30 and 40 degrees in the temporal field (p < 0.038). An increase in astigmatism with correction was observed for J45 (p < 0.05) was also seen in eyes with moderate myopia, but this was limited to the nasal field. Previous investigators have suggested that peripheral hyperopic defocus may play a role in the development and progression of myopia. We have shown that SVLs used to correct myopia can result in increased hyperopic defocus at the peripheral retina in the eyes of Chinese children. The magnitude of this increase tends to escalate with increasing refractive error and eccentricity, especially in cases with moderate levels of myopia.

Layer-Dependent Loss and Enhancement of Geniculostriate and Retinotectal Pathways in Adult Human Amblyopia

To investigate the relationship between the subjectively experienced misperceptions and the objectively determined two-dimensional spatial displacement maps in subjects with strabismic and anisometropic amblyopia. Seventeen experimental subjects were asked to describe and sketch their perception of simple geometric pattern, as perceived through their amblyopic eyes. A subgroup of 15 subjects participated in a psychophysical experiment, in which the two-dimensional displacement maps were determined by asking the subjects to reconstruct, point-by-point, memorized circles of different radii. The results of these displacement maps were related to the clinical characteristics and the perceptual descriptions of the same subjects. Twelve of the 17 investigated subjects experienced spatial distortions; six subjects perceived temporal instabilities, either in addition, or in the absence of spatial distortions. Objectively determined spatial displacement and spatial uncertainty were significantly larger in subjects with a history of strabismus and a deep acuity loss than in subjects with refractive etiology and a mild acuity loss. Subjects experiencing temporal instability showed more spatial uncertainty in the amblyopic eye than did subjects with a stable perception. These results suggest that a history of strabismus and a deep amblyopia are more likely to be associated with temporal misperceptions than a refractive etiology and a mild acuity loss. A temporally unstable perception may be related to a more profound disorganization of the central neural pathways connected to the amblyopic eye.

Kittens raised with different kinds of abnormal early visual experience (monocular and binocular deprivation, convergent strabismus, eye rotation, asymmetric alternating occlusion, early callosal split) show systematic deficits in the nasal visual field of the affected eye. To test whether abnormal visual experience produces similar deficits in the human visual system, we measured the monocular visual field of humans with subnormal binocular vision (strabismic and anisometropic amblyopes, strabismics with alternating fixation). Eight amblyopes were tested with a computer-assisted static perimetry (Octopus 2000). Twenty other subjects were tested with kinetic perimetry (Goldmann 940), 11 subjects with static perimetry (Goldmann 940). In some of these subjects, we measured the latency of saccades and the accuracy of visually guided pointing toward stimuli presented in the peripheral visual field. Both strabismic and anisometropic amblyopes frequently showed deficits of visual sensitivity in the central part of the visual field, but no systematic deficits in the peripheral field of the amblyopic eyes. Strabismic alternators had practically equal fields in the two eyes. Neither saccadic latency nor pointing accuracy showed a systematic impairment in the nasal visual field. The discrepancy between the field losses in strabismic humans and in cats raised with a surgically induced squint cannot be due to methodological differences, but rather to anatomical differences, or to the different origin of strabismus in the two species.

A pilot study was undertaken to address the tolerance and efficacy of levodopa/carbidopa treatment for amblyopia in older amblyopic children who failed to respond to conventional occlusion therapy. Five amblyopic children, between the ages of 7 and 12 years, and two normal adults were given between 100 mg/25 mg and 400 mg/100 mg of levodopa/carbidopa, respectively, depending on body weight. A symptoms questionnaire was completed, with temperature, respiration, heart rate, and blood pressure taken periodically to assess tolerance. Blood samples were taken, via a heparin well, to assess the pharmacokinetics of levodopa, dopamine, noradrenaline, and DOPAC. Snellen visual acuity, contrast sensitivity, stereo acuity, and pattern VERs were measured periodically to assess efficacy. The results revealed a high prevalence of side effects including emesis and nausea (four of seven subjects). Pharmacokinetics revealed that maximum serum levels of levodopa occurred 30 minutes to 1 hour after drug ingestion and decreased by 50% after 2 to 4 hours. One hour after drug ingestion, Snellen visual acuity temporarily improved from an average of 20/159 to 20/83 in the amblyopic eyes. Contrast sensitivity and pattern VERs (10-minute checks) temporarily improved in both dominant and amblyopic eyes, whereas visual function remained stable in normal eyes. The improvements in visual function started to decrease 5 hours after drug ingestion. The results are discussed in the context of developing a therapeutic trial of levodopa/carbidopa for childhood amblyopia.

Further studies were made of the simultaneous comparison mechanism used by hatchling green turtles, Chelonia mydas, in sea-finding behaviour. The aim was to learn if visual inputs from different directions, stimulating different parts of the retina, had the same effects on orientation. To do this goggles were designed that permitted occlusion of parts of the visual field. Wearing goggles did not in itself affect orientation. When the nasal visual field for one eye and the temporal field for the other eye were covered, turtles circled consistently in the direction of the eye with the nasal occlusion. The total numbers of circles made in a given time by such turtles were not significantly different from those made by animals with simple unilateral blindfolds. Covering the temporal field of one eye resulted in some, though not all, turtles turning contralateral to that eye, provided the other eye was totally covered. On the whole the data were consistent with the idea that inputs in the nasal field are associated with contralateral turning and those in the temporal field with ipsilateral turning. Some complications to this interpretation are also discussed. However, the results demonstrate unequivocally that inputs from different directions contribute differently to sea-finding orientation of green turtles.