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Amblyopia characterization, treatment, and prophylaxis.

Abstract

Amblyopia has a 1.6-3.6% prevalence, higher in the medically underserved. It is more complex than simply visual acuity loss and the better eye has sub-clinical deficits. Functional limitations appear more extensive and loss of vision in the better eye of amblyopes more prevalent than previously thought. Amblyopia screening and treatment are efficacious, but cost-effectiveness concerns remain. Refractive correction alone may successfully treat anisometropic amblyopia and it, minimal occlusion, and/or catecholamine treatment can provide initial vision improvement that may improve compliance with subsequent long-duration treatment. Atropine penalization appears as effective as occlusion for moderate amblyopia, with limited-day penalization as effective as full-time. Cytidin-5'-diphosphocholine may hold promise as a medical treatment. Interpretation of much of the amblyopia literature is made difficult by: inaccurate visual acuity measurement at initial visit, lack of adequate refractive correction prior to and during treatment, and lack of long-term follow-up results. Successful treatment can be achieved in at most 63-83% of patients. Treatment outcome is a function of initial visual acuity and type of amblyopia, and a reciprocal product of treatment efficacy, duration, and compliance. Age at treatment onset is not predictive of outcome in many studies but detection under versus over 2-3 years of age may be. Multiple screenings prior to that age, and prompt treatment, reduce prevalence. Would a single early cycloplegic photoscreening be as, or more, successful at detection or prediction than the multiple screenings, and more cost-effective? Penalization and occlusion have minimal incidence of reverse amblyopia and/or side-effects, no significant influence on emmetropization, and no consistent effect on sign or size of post-treatment changes in strabismic deviation. There may be a physiologic basis for better age-indifferent outcome than tapped by current treatment methodologies. Infant refractive correction substantially reduces accommodative esotropia and amblyopia incidence without interference with emmetropization. Compensatory prism, alone or post-operatively, and/or minus lens treatment, and/or wide-field fusional amplitude training, may reduce risk of early onset esotropia. Multivariate screening using continuous-scale measurements may be more effective than traditional single-test dichotomous pass/fail measures. Pigmentation may be one parameter because Caucasians are at higher risk for esotropia than non-whites.

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BibTeXRIS

Kurt Simons. Amblyopia characterization, treatment, and prophylaxis.. https://doi.org/10.1016/j.survophthal.2004.12.005

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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↗

Detection of abnormal visual cortex in children with amblyopia by voxel-based morphometry.

PURPOSE: To detect the abnormalities of gray matter in children with amblyopia by voxel-based morphometry (VBM). DESIGN: Prospective, nonrandomized clinical trial. METHODS: Thirteen children with amblyopia and 14 normally sighted children underwent magnetic resonance (MR) examination. The two groups were age-matched with a mean age of 5.8 years. In the amblyopia group, five children had strabismus amblyopia, and eight had anisometropic amblyopia. We analyzed the original 3-dimensional T1 brain images using the VBM module within the widely used analysis software package SPM2 (Welcome Department of Cognitive Neurology, London, United Kingdom). After normalization, segmentation, and smoothing of the images, comparison between amblyopic and control groups was derived for the gray matter of the entire brain using parametric statistics. RESULTS: The results of VBM analysis indicated that the amblyopic group had decreased gray matter density in the middle frontal gyrus, parahippocampal gyrus, fusiform gyrus, inferior temporal gyrus of the left hemisphere, and the bilateral calcarine cortices. The radii of these regions ranged from 12 to 36 voxels. These abnormalities were consistent with morphologic changes in brain regions related to visual function. CONCLUSIONS: Using MR and VBM analysis, we detected morphologic changes in the visual cortex of children with amblyopia, which may indicate developmental abnormalities of visual cortex during the critical growth period.

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