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PubMed2001

The Rotterdam AMblyopia Screening Effectiveness Study (RAMSES): compliance and predictive value in the first 2 years.

BACKGROUND: RAMSES is a 7 year follow up study, aiming at the evaluation of the effectiveness and the efficiency of screening for amblyopia. In this first report, concerning the first 2 years of life, the compliance with the prevention programme and the positive predictive value (PPV) of the screening tests used, are presented. METHODS: All results of the standardised screening test for strabismus, applied by child healthcare physicians, within a birth cohort of 4072 Rotterdam children at the age of 9, 14, and 24 months, were registered. Children with a positive test result were referred to their general practitioner, who was asked to arrange a definitive referral to an ophthalmological centre. The results of the examinations at these centres were registered in standardised forms and served as reference for establishing the PPV. RESULTS: The screening was (at least one time) attended by 3958 children (97%). 160 of these children (4%) were referred, of whom 101 (64%) visited an ophthalmological centre, so that a conclusive diagnostic evaluation was possible. For amblyopia, the predictive value of a positive test result followed by an effective referral was 0.42. CONCLUSION: Referral procedures after a positive test result in the Dutch child healthcare screening programme for amblyopia need to be improved. The Dutch screening test used to detect amblyopia exhibits a relatively favourable PPV.

Amblyopia↗
PubMed2000

Successful amblyopia therapy initiated after age 7 years: compliance cures.

OBJECTIVE: To report successful therapy for anisometropic and strabismic amblyopia initiated after age 7 years. METHODS: A consecutive series of 36 compliant children older than 7 years (range, 7.0 to 10.3 years; mean, 8.2 years) at initiation of amblyopia therapy for anisometropic (19 patients; mean age, 8.3 years), strabismic (9 patients; mean age, 8.0 years), or anisometropic and strabismic (8 patients; mean age, 8.0 years) amblyopia was studied. Initial (worst) visual acuities were between 20/50 and 20/400 (log geometric mean, -0.83 [antilog, 20/134] for all patients; -0.88 [antilog, 20/151] for anisometropic patients; -0.70 [antilog, 20/100] for strabismic patients; and -0.88 [antilog, 20/151] for anisometropic and strabismic patients). Initial (worst) binocularity was absent or reduced in all cases. Therapy consisted of (1) full-time standard occlusion (21 patients; mean age, 8.0 years), (2) total penalization (7 patients; mean age, 7.8 years), or (3) full-time occlusive contact lenses (8 patients; mean age, 8.8 years). RESULTS: Final (best) visual acuities were between 20/20 and 20/30 for all 36 patients. Final (best) binocularity was maintained or improved for 22 (61%) of 36 patients, including 16 anisometropic patients (84%), 2 strabismic patients (22%), and 4 anisometropic and strabismic patients (50%). CONCLUSION: Given compliance, therapy for anisometropic and strabismic amblyopia can be successful even if initiated after age 7 years. Arch Ophthalmol. 2000;118:1535-1541

Amblyopia↗
PubMed1987

Unilateral peripapillary myelinated nerve fibers with myopia and/or amblyopia.

This report describes 12 patients with unilateral peripapillary myelinated nerve fibers associated with myopia and/or amblyopia. Seven patients had myopia with a mean of -13.00 diopters of anisometropia and abnormal maculae varying from a decreased reflex to pigment dispersion. These patients had final visual acuities of 20/200 or less following conventional amblyopia therapy. In contrast, five patients had myopia with a mean of -3.75 diopters of anisometropia and normal maculae. These patients had final visual acuities of 20/30 or greater with identical therapy. There was a statistically significant difference between the mean diopters of anisometropia of these two groups. However, the range of diopters of anisometropia overlapped, and the critical feature that determined which patients could achieve good vision was the macular appearance. This condition is distinct from simple unilateral myopia with amblyopia and from myelinated nerve fibers without myopia or amblyopia.

Amblyopia↗
PubMed1983

Practical management of amblyopia.

Our knowledge on the mechanism of amblyopia has gained in recent years from concerted research efforts in basic science and clinical laboratories. Different clinical forms of amblyopia are reviewed and their diagnostic and therapeutic significance discussed. In spite of etiologic differences there are pathophysiological similarities. The value of the time proven constant occlusion treatment of the sound eye remains unchallenged even though minor modifications have become necessary to prevent occlusion amblyopia in infants and young children. Part-time occlusion and penalization are of ancillary value but cannot be considered equal in effectiveness to constant occlusion. Due to increasing public awareness there is a trend toward earlier diagnosis and thus successful treatment of amblyopia. However, more efforts must be directed toward including newborns in visual screening examinations.

Amblyopia↗
PubMed1986

Central and peripheral residual vision in humans with bilateral deprivation amblyopia.

Residual visual capacities were investigated in the central and peripheral visual fields of 13 patients with bilateral deprivation amblyopia secondary to congenital cataracts removed at an early age. In comparison with a control group of normal subjects, spatial modulation sensitivity function of the amblyopes was markedly impaired in each experimental condition, i.e. both when the stimuli were stationary or drifting (8 Hz) gratings and both in central or peripheral visual field, at 10 and 20 degrees eccentricity. The sensitivity drop was observed over the whole spatial frequency range, although it was much more severe at high frequencies. Threshold elevation, with respect to controls, was very similar in conditions using stationary or drifting gratings, suggesting that both sustained and transient mechanisms are affected by stimulus deprivation amblyopia. Temporal modulation sensitivity function was uniformly impaired over the whole temporal frequency range. When compared with other types of amblyopia, this pattern of spatiotemporal sensitivity loss appeared characteristic of deprivation amblyopia. The peripheral deficit was particularly striking by its severity and extent, as ascertained by static perimetry and visual acuity measurements up to 50 degrees eccentricity. This finding emphasizes the susceptibility of peripheral as well as central human vision to early deprivation and suggests that peripheral visual functions are still immature in newborns. Finally, the overall deficit varied with the severity of the deprivation, in that patients with complete neonatal cataract performed much worse than those with incomplete cataract.

Adolescent↗
PubMed1983

Oblique effects, vertical effects and meridional amblyopia in monkeys.

Orientation anisotropies were investigated for monkeys with normal visual acuity and for monkeys with experimentally induced amblyopia. It was found that the majority of control monkeys showed a normal oblique effect if any existing refractive errors were carefully corrected, but a few of the control monkeys had a meridional amblyopia, i.e., an orientation anisotropy in which the grating orientation for the greatest and lowest contrast sensitivities were correlated with the principal meridians of an astigmatic refractive error even when the refractive error was corrected. For monkeys with strabismic amblyopia caused by a surgically induced divergent strabismus, the orientation anisotropies showed a vertical effect in which contrast sensitivity was lower for vertically oriented gratings than for horizontally oriented gratings. However, monkeys with the same degree of amblyopia resulting from experimental procedures that did not involve a misalignment of the visual axes showed orientation anisotropies that corresponded to the usual oblique effect.

Amblyopia↗
PubMed1989

Amblyopia revisited: evidence for the heterogeneity of the syndrome.

Functional amblyopia has been considered as a homogeneous syndrome for the last decade or so, mainly on the basis of animal experiments. Recently, important differences have been shown to exist between strabismic and anisometropic as well as deprivation amblyopia. Even strabismic amblyopia may be subdivided in different classes. These statements are supported with experimental and clinical data. Clinical relevance of the heterogeneity of amblyopia is discussed particularly in the view of the concept of its cure.

Amblyopia↗
PubMed2005

Evaluating reading acuity and speed in children with microstrabismic amblyopia using a standardized reading chart system.

BACKGROUND: To examine if standardized reading charts with highly comparable test items can be used for evaluating impairments in the monocular reading performance of children with microstrabismic amblyopia characterized by a small angle of squint with less than 5 degrees. METHODS: The reading performance of 22 children (mean age: 11.7+/-1.6 years) with unilateral microstrabismic amblyopia was evaluated monocularly in both eyes, using standardized reading charts for the simultaneous determination of reading acuity and speed. The print sizes of the highly comparable sentence optotypes were logarithmically graded, providing constant geometric proportions for all testing distances in order to control contour interaction. All children were under continuous amblyopia therapy. RESULTS: In the amblyopic eyes, reading acuity and maximum reading speed were significantly impaired when compared to the sound fellow eyes (P<0.001). In respect of the maximum reading speed, a mean inter-ocular difference of 33+/-19 words per minute was found, revealing functionally relevant deficits in monocular reading performance. The amblyopic eyes achieved only a significantly reduced reading acuity (mean inter-ocular difference: LogRAD 0.5+/-0.24; P<0.001). In eight children, the amblyopic eyes achieved a best-corrected visual acuity of LogMAR 0.0 or better: in respect of the visual acuity, there was no significant inter-ocular difference, but reading acuity and maximum reading speed were significantly impaired when compared to the fellow eyes. CONCLUSIONS: Microstrabismic amblyopia was associated with significant impairment of reading acuity and speed in treated amblyopes, even in those with no persistent acuity deficit. To improve treatment addressing these functional deficits, reading performance should be monitored over time using standardized reading tests, which provide essential information about functionally relevant reading impairments.

Amblyopia↗
PubMed1986

Pattern-reversal visual-evoked potentials in the diagnosis of amblyopia in children.

We assessed the potential clinical usefulness of pattern-reversal visual-evoked potentials in the diagnosis of amblyopia. Twenty-seven children with anisometropic amblyopia and four children without amblyopia participated. Estimates of visual acuity for each eye (Snellen visual acuity) were obtained by conventional psychometric methods. Visual-evoked potentials to reversing checks subtending 15 minutes of visual arc were also obtained. Visual-evoked potential testing and interpretation were done in a masked fashion. Ten of the 31 children were retested seven to 21 days after the first test to estimate reliability of the procedures. Of the 27 amblyopic children, 22 were correctly identified by the visual-evoked potential test alone. In four patients initial visual-evoked potential tests failed to identify the disparity in visual acuity between the eyes and retests in two of the four again had false-negative results. In one child initial visual-evoked potential testing incorrectly identified the amblyopic eye but repeat testing did identify it. Of the four children with symmetrically good vision, three were correctly identified as normal by the initial visual-evoked potential test. The other normal child was incorrectly identified by the visual-evoked potential test as having amblyopia.

Adolescent↗
PubMed1992

The spatial localization deficit in amblyopia.

There have now been numerous reports of a spatial localization deficit in amblyopia but none so far have tackled (1) the relationship between the contrast sensitivity and spatial localization deficits and (2) whether the spatial localization deficit is best described in units of visual angle or in terms of the underlying filter size. These issues are germane because they lie at the very heart of our understanding of the underlying deficit in amblyopia. To answer these questions we use spatially bandpass stimuli so that we can readily compare detection and localization for the same stimuli at each of a number of spatial scales. For some amblyopes (all strabismics and a minority of anisometropes) the contrast sensitivity defect neither underlies nor covaries with the spatial localization deficit. In the majority of anisometropic amblyopes, the contrast sensitivity loss is a complete description. The spatial localization deficit in amblyopia is of two independent kinds; positional inaccuracy and positional distortion. The positional inaccuracy deficit which can occur in varying degrees in both strabismic and anisometropic amblyopia, affects all spatial scales equally and therefore is best thought of in terms of a constant fraction of the underlying filter size in the space-frequency plane. The positional distortion deficit which can also occur to varying degrees in both strabismic and anisometropic forms can not be easily understood within this metric at least for strabismics.

Amblyopia↗
PubMed1994

Is the spatial deficit in strabismic amblyopia due to loss of cells or an uncalibrated disarray of cells?

We examine two competing explanations for the spatial localization deficit in human strabismic amblyopia, namely neural undersampling and uncalibrated neural disarray. An undersampling hypothesis would predict an associated deficit for contrast discrimination for which we find no evidence in strabismic amblyopia. A neural disarray hypothesis would predict an associated deficit in the degree to which stimuli appear spatially distorted. We find evidence for such a deficit in strabismic amblyopia. We propose that the spatial deficit in strabismic amblyopia is due to a filter-based distortion which is unable to be re-calibrated by higher visual centres.

Amblyopia↗
PubMed1983

Animal models of strabismic amblyopia: comparative behavioral studies.

Visual acuity and visuo-motor behavior were assessed in various models of experimental amblyopia in cats (n = 15). Three models of strabismic amblyopia were studied: surgical esotropia by sectioning one lateral rectus muscle; comitant optical strabismus by rearing cats with goggles which placed a stationary wedge prism before one eye; and incomitant optical strabismus by rearing cats with goggles which placed a rotatable wedge prism before one eye. These cats were compared with normal and monocularly deprived cats. Clear amblyopic deficits were found in monocularly deprived, esotropic and rotating prism cats. The amblyopic deficits were graded among these preparations, being most severe in monocularly deprived cats and least severe in esotropic cats. The degree of behavioral amblyopia in these preparations was correlated with the extent of physiological abnormalities in visual cortex and the lateral geniculate nucleus. Fixed optical strabismus did not result in behavioral deficits and does not appear to be a good model of strabismic amblyopia. Variable optical strabismus, on the other hand, produced clear deficits in one eye, both behaviorally and physiologically, without impaired ocular motility.

Amblyopia↗
PubMed2005

Pediatric Amblyopia Risk Investigation Study (PARIS).

PURPOSE: To assess the learning curve, testability, and reliability of vision screening modalities administered by pediatric health extenders. DESIGN: Prospective masked clinical trial. METHODS: Two hundred subjects aged 3 to 6 underwent timed screening for amblyopia by physician extenders, including LEA visual acuity (LEA), stereopsis (RDE), and noncycloplegic autorefraction (NCAR). Patients returned for a comprehensive diagnostic eye examination performed by an ophthalmologist or optometrist. RESULTS: Average screening time was 5.4 +/- 1.6 minutes (LEA), 1.9 +/- 0.9 minutes (RDE), and 1.7 +/- 1.0 minutes (NCAR). Test time for NCAR and RDE fell by 40% during the study period. Overall testability was 92% (LEA), 96% (RDE), and 94% (NCAR). Testability among 3-year-olds was 73% (LEA), 96% (RDE), and 89% (NCAR). Reliability of LEA was moderate (r = .59). Reliability of NCAR was high for astigmatism (Cyl) (r = .89), moderate for spherical equivalent (SE) (r = .66), and low for anisometropia (ANISO) (r = .38). Correlation of cycloplegic autorefraction (CAR) with gold standard cycloplegic retinoscopic refraction (CRR) was very high for SE (.85), CYL (.77), and moderate for ANISO (.48). CONCLUSIONS: With NCAR, physician extenders can quickly and reliably detect astigmatism and spherical refractive error in one-third the time it takes to obtain visual acuity. LEA has a lower initial cost, but is time consuming, moderately reliable, and more difficult for 3-year-olds. Shorter examination time and higher reliability may make NCAR a more efficient screening tool for refractive amblyopia in younger children. Future study is needed to determine the sensitivity and specificity of NCAR and other screening methods in detecting amblyopia and amblyopia risk factors.

Amblyopia↗
PubMed2005

Suppression of metabolic activity caused by infantile strabismus and strabismic amblyopia in striate visual cortex of macaque monkeys.

INTRODUCTION: Suppression is a major sensorial abnormality in humans and monkeys with infantile strabismus. We previously reported evidence of metabolic suppression in the visual cortex of strabismic macaques, using the mitochondrial enzyme cytochrome oxidase as an anatomic label. The purpose of this study was to further elucidate alterations in cortical metabolic activity, with or without amblyopia. MATERIALS AND METHODS: Six macaque monkeys were used in the experiments (four strabismic and two control). Three of the strabismic monkeys had naturally occurring, infantile strabismus (two esotropic, one exotropic). The fourth strabismic monkey had infantile microesotropia induced by alternating monocular occlusion in the first months of life. Ocular motor behaviors and visual acuity were tested after infancy in each animal, and development of stereopsis was recorded during infancy in one strabismic and one control monkey. Ocular dominance columns (ODCs) of the striate visual cortex (area V1) were labeled using cytochrome oxidase (CO) histochemistry alone, or CO in conjunction with an anterograde tracer ([H 3 ]proline or WGA-HRP) injected into one eye. RESULTS: Each of the strabismic monkeys showed inequalities of metabolic activity in ODCs of opposite ocularity, visible as rows of lighter CO staining, corresponding to ODCs of lower metabolic activity, alternating with rows of darker CO staining, corresponding to ODCs of higher metabolic activity. In monkeys who had infantile strabismus and unilateral amblyopia, lower metabolic activity was found in (suppressed) ODCs driven by the nondominant eye in each hemisphere. In monkeys who had infantile esotropia and alternating fixation (no amblyopia), metabolic activity was lower in ODCs driven by the ipsilateral eye in each hemisphere. The suppression included a monocular core zone at the center of ODCs and binocular border zones at the boundaries of ODCs. This suppression was not evident in the monocular lamina of the LGN, indicating an intracortical rather than subcortical mechanism. CONCLUSION: Suppression of metabolic activity in ODCs of V1 differs depending upon whether infantile strabismus is alternating or occurs in conjunction with unilateral amblyopia. Our findings reinforce the principle that unrepaired strabismus promotes abnormal competition in V1, observable as interocular suppression of ODCs.

Amblyopia↗
PubMed2005

The effects of L-dopa on the functional magnetic resonance imaging response of patients with amblyopia: a pilot study.

PURPOSE: We investigated the effects of a single dose of levodopa (L-dopa) on the level and extent of visual cortex activation of subjects with amblyopia and normal subjects using blood oxygenation level-dependent functional magnetic resonance imaging (fMRI). SUBJECTS AND METHODS: Six patients with amblyopia and 9 control patients were recruited. A baseline fMRI session was followed by a second session 90 minutes after the dose of L-dopa. Visual stimuli included vertical sinusoidal gratings with spatial frequencies of 1 and 2 cpd that were counterphased at 4 Hz. Stimuli were presented monocularly and binocularly. The fMRI response was characterized by the total volume and the average level of activation within the occipital cortex. An interocular absolute difference (IDIF) was defined in terms of said measures for between-population analysis of monocular data. RESULTS: After the administration of L-dopa, visual acuity improved significantly ( P = 0.026) from 0.72 +/- 0.21 (mean +/- SD) to 0.64 +/- 0.24 LogMAR in the amblyopic eye, although remaining the same in the dominant eye and in the eyes of control subjects. The response to L-dopa was found to be population-specific, as indicated by a significant treatment-by-population interaction for the volume of activation IDIF ( P = 0.018) measure: subjects with amblyopia exhibited a post-treatment increase in the volume of activation IDIF whereas control subjects showed a less prominent decrease. This post-treatment increase of IDIF in subjects with amblyopia may be explained by the decrease in the volume of activation found for the amblyopic eye after L-dopa ( P = 0.038). No L-dopa-related activation changes were detected for dominant eye or binocular stimulation in the amblyopic group, and no change was detected in control subjects. CONCLUSION: L-dopa elicits a population-specific modulation of the fMRI response, namely, a reduced total volume of activation from the amblyopic eye despite improvement in visual acuity.

Adolescent↗
PubMed2026

Genome-Wide and Rare Variant Association Studies of Amblyopia in Admixed American and African Ancestry Groups.

OBJECTIVE: To identify genetic variants associated with amblyopia in African (AFR) and Admixed American (AMR) ancestry groups, expanding on previous studies conducted in European ancestry. DESIGN: Retrospective ancestry-stratified genome-wide association study (GWAS) and gene-level rare variant association study (RVAS). PARTICIPANTS: Participants in the All of Us Research Program from AFR and AMR ancestry groups who had whole-genome sequencing available. Cases and controls were distinguished based on the presence of International Classification of Diseases 9/10/SNOMED diagnosis codes for amblyopia in electronic health records. This yielded ancestry-stratified subsets of 269 cases and 71 585 controls of AMR ancestry and 366 cases and 79 460 controls of AFR ancestry. METHODS: Stratified logistic regression models were adjusted for age, biological sex, and the top 10 principal components of genomic ancestry. GWAS was limited to common variants (minor allele frequency &#x2265;1%), and RVAS was limited to rare variants with coding sequence-altering effects (minor allele frequency >1%, exonic only, excluding synonymous variants) aggregated at the gene level using the SKAT algorithm. Downstream analyses of the significant variants were performed using KEGG and GO pathway analysis and STRING database queries for protein-protein interactions and gene-gene interactions. MAIN OUTCOME MEASURES: Single-nucleotide polymorphisms were determined to have genome-wide significance if P < 5e-8 in the GWAS, and genes were determined to have significant association with amblyopia in the RVAS if P < 8.0 &#xd7; 10-4. RESULTS: In the AMR GWAS, 245 unique single-nucleotide polymorphisms mapping to 97 distinct loci were identified, notably within neurodevelopmental and axonal guidance genes, including ROBO1, SEMA4B, PTPRD, NRXN1, and CAMK2D. The AFR GWAS identified 11 significant variants corresponding to 6 loci mapping primarily to long noncoding RNAs and pseudogenes. The AMR RVAS identified 15 genes, including axonal transport genes (KIF1B and KIF7) and growth factor signaling genes (EGF, ERBIN, and AKAP17A). The AFR RVAS identified a single gene, DLG2, which encodes the postsynaptic protein PSD-93, which promotes the closure of the sensitive period of neuroplasticity for vision in early childhood. CONCLUSIONS: Genetic risk architectures for amblyopia differ across ancestries but fundamentally converge on neurodevelopmental signaling, cortical synapse assembly, and sensitive period plasticity rather than ocular structural dynamics. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Amblyopia↗
PubMed2004

Altered global shape discrimination in deprivation amblyopia.

To assess the effect of deprivation amblyopia on global shape discrimination, sensitivity to radial deformation of circular patterns was assessed in patients treated for congenital (N=7) or developmental (N=1) cataracts. Elevation in radial deformation threshold was dependent on circular contour frequency and the depth of amblyopia. Analysis of thresholds expressed as Weber fractions indicated a shift in global integration to a larger scale. In a pedestal experiment, equivalent intrinsic noise increased in proportion to the depth of amblyopia. The results suggest neural undersampling in V1 and/or higher visual cortical areas in deprivation amblyopia and a possible role for neural disarray.

Adolescent↗
PubMed2000

Phakic posterior chamber intraocular lens for the correction of anisometropia and treatment of amblyopia.

PURPOSE: To assess the potential visual benefits of posterior chamber phakic intraocular lens implants in eyes of children with anisometropic amblyopia. METHODS: In a prospective study, three girls 9, 14, and 18 years old with high anisometropia and deep amblyopia were included in this study. The phakic posterior chamber intraocular lens (ICL; STAAR Surgical AG, Nidau, Switzerland) was used to correct the anisometropia. This intraocular lens was inserted in the anterior chamber through a 3.0-mm temporal clear cornea incision and manipulated into the posterior chamber using an iris manipulator. A peripheral iridectomy was performed using the Ocutome Probe (Storz; Premiere, St. Louis, Missouri). Local therapy with corticosteroids and antibiotics were prescribed for 2 weeks, and patients were followed regularly for a period of 6 to 9 months. RESULTS: In the three amblyopic eyes of the three patients, the preoperative best-corrected visual acuity of 6/30, 6/60, and 6/30 improved, to 6/7.5 (20/25), 6/30 (20/100), and 6/15 (20/50), respectively, 6 months after the surgery. Binocular functions with development of fusional abilities and stereopsis were observed in two of these patients after the intraocular lens implantation. In the third patient, the fusional abilities developed only after surgical correction of the exotropia. The intraocular pressure remained within normal limits, and there was no significant change in the corneal endothelial cell count during the period of follow-up. No major intraoperative or postoperative complications were observed, except for a temporary pigment dispersion. CONCLUSIONS: Implantation of phakic posterior chamber intraocular lenses may be beneficial for the treatment of amblyopia in children with anisometropia. Although additional cases and long-term follow-up observations are necessary, it appears that amblyopia may be overcome by the use of posterior chamber phakic intraocular lens implants, even in eyes of children beyond the age generally considered to be responsive to anti-amblyopic treatment.

Adolescent↗