PubMed · 4647809
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S Delthil, J Sourdille. Screening for amblyopia.. https://pubmed.ncbi.nlm.nih.gov/4647809/
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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 ≥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 × 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.
Monocular contrast sensitivity (CS) measurements were obtained in the two principal meridians of eight constant unilateral strabismic subjects and four subjects diagnosed with alternating strabismus. The results indicated that: (1) the CS of both the fellow and deviating eyes of patients with a constant unilateral deviation is significantly less than that of visually normal eyes at high spatial frequencies; (2) both the fellow and deviating eyes reveal a significant reduction in CS to vertically oriented gratings. This effect is frequency-specific, occurring only at the highest spatial frequencies; (3) the magnitude of the orientation anisotropy did not vary systematically with the degree of amblyopia; and (4) a mild orientation anisotropy was observed in only three of the eight alternating strabismic eyes tested. The etiology of the vertical effect is examined with respect to the role of anomalous binocular competition, suppression and abnormal eye movements.
Neural interactions between widely separated stimuli were explored with psychophysical and visual evoked potential (VEP) measures in normal and amblyopic observers. Contrast detection thresholds were measured psychophysically for small foveally viewed Gabor patches presented in isolation and in the presence of similar, but laterally displaced flanks. The amplitude and phase of VEPs elicited by similar targets were also measured. The presence of neural interaction between the target and flank responses was assessed by comparing the unflanked threshold to the flanked threshold in the psychophysical experiments and by comparing the response predicted by the algebraic sum of test and flank responses to that measured when test and flanks were presented simultaneously. In normal observers simultaneous presentation of test and flank targets produces a VEP response that is up to a factor of two larger than the linear prediction (facilitation). Psychophysical threshold is also facilitated by a comparable factor. Facilitation was found mainly for configurations in which local (carrier) and global (patch) orientations resulted in collinearity, independent of global orientation (meridian). Amblyopic observers showed several deviations from the normal pattern. The facilitation for the collinear configurations was either markedly lower than normal or was replaced by inhibition. The normal pattern of spatial interaction may facilitate the grouping of collinear line segments into smooth curves. In contrast, abnormal long-range spatial interactions may underlie the grouping disorders and perceptual distortions found in amblyopia.