Myopia control utilizing low-dose atropine as an isolated therapy or in combination with other optical measures: A retrospective cohort study

PURPOSE: To assess the additive potency of low-dose atropine combined with optical measures designed to decrease myopia progression. MATERIALS AND METHODS: This retrospective study included 104 myopic children aged 5–12 over 4 years, divided into five groups: daily instillation of 0.01% atropine and distance single-vision spectacles (A), 0.01% atropine and progressive addition lenses (A + PAL), 0.01% atropine and soft contact lens with peripheral blur (A + CL). Two control groups were included, prescribed bifocal spectacles or single vision (SV) spectacles. Cycloplegic spherical equivalence refraction was measured biannually, including 1 year after cessation of treatment. RESULTS: A significant decrease in myopia progression was noted during the 2nd and 3rd years of atropine treatment: A −0.55 ± 0.55D, −0.15 ± 0.15, −0.12 ± 0.12D were 1st, 2nd, 3rd years, respectively, A + PAL −0.47 ± 0.37D, −0.10 ± 0.25D, and −0.11 ± 0.25D were 1st, 2nd, 3rd years, respectively, A + CL −0.36 ± 0.43D, −0.13 ± 0.29D, and −0.10 ± 0.27D were 1st, 2nd, 3rd years, respectively. Myopia progression over 3 years, respectively, was −0.82 ± 0.50D, −0.70 ± 0.69D, −0.59 ± 0.66D in the bifocal group and −1.20 ± 1.28D, −0.72 ± 0.62D, −0.65 ± 0.47D in the SV group. One year after cessation of atropine treatment, myopia progression was − 0.32 ± 0.31D in A, −0.23 ± 0.28D in A + PAL, and −0.18 ± 0.35D in A + CL. CONCLUSION: Atropine 0.01% presented as effective at decelerating myopia progression, more prominent in the 2nd and 3rd years of treatment. Combining atropine 0.01% with optical modalities exhibited a trend for added efficacy over monotherapy. A + CL exhibited the least rebound effect 1 year after cessation of treatment

A Missense Mutation in the LIM2 Gene Is Associated with Autosomal Recessive Presenile Cataract in an Inbred Iraqi Jewish Family

In an inbred Iraqi Jewish family, we have studied three siblings with presenile cataract first noticed between the ages of 20 and 51 years and segregating in an autosomal recessive mode. Using microsatellite repeat markers in close proximity to 25 genes and loci previously associated with congenital cataracts in humans and mice, we identified five markers on chromosome 19q that cosegregated with the disease. Sequencing of LIM2, one of two candidate genes in this region, revealed a homozygous T→G change resulting in a phenylalanine-to-valine substitution at position 105 of the protein. To our knowledge, this constitutes the first report, in humans, of cataract formation associated with a mutation in LIM2. Studies of late-onset single-gene cataracts may provide insight into the pathogenesis of the more common age-related cataracts

Rare Genetic Variants in Jewish Patients Suffering from Age-Related Macular Degeneration

Purpose: To identify rare genetic variants in early age-related macular degeneration (AMD) utilizing whole-exome sequencing (WES). Methods: Eight non-related early-AMD families of different Jewish ethnicities were ascertained. Initial mutation screening (phase-1) included common complement factor-H (CFH) p.Y402H; and age related maculopathy susceptibility 2 (ARMS2) p.A69S; and rare variants complement factor-I (CFI) p.V412M; and hemicentin1 (HMCN1) c.4163delC identified previously in our population. Four families, whose initial screening for the aforementioned variants was negative, underwent WES (phase-2). Bioinformatics filtering was based on functionality (from a panel of 234 genes with proven or presumed association to AMD); predicted severity; and frequency (rare variants with minor allele frequency <1%). When applicable, further screening for specific rare variants was carried out on additional cases of similar ethnicities and phenotypes (phase-3). Results: Phase-1 identified three families carrying CFI p.V412M mutation. WES analysis detected probable disease-related variants in three out of the remaining families. These included: a family with a variant in PLEKHA1 gene p.S177N; a family with previously reported variant p.R1210C in CFH gene; and two families with the C3 p.R735W variant. Conclusions: Rare, high-penetrance variants have a profound contribution to early-AMD pathogenesis. Utilization of WES in genetic research of multifactorial diseases as AMD, allows a thorough comprehensive analysis with the identification of previously unreported rare variants

Mutations in FYCO1 Cause Autosomal-Recessive Congenital Cataracts

Congenital cataracts (CCs), responsible for about one-third of blindness in infants, are a major cause of vision loss in children worldwide. Autosomal-recessive congenital cataracts (arCC) form a clinically diverse and genetically heterogeneous group of disorders of the crystalline lens. To identify the genetic cause of arCC in consanguineous Pakistani families, we performed genome-wide linkage analysis and fine mapping and identified linkage to 3p21-p22 with a summed LOD score of 33.42. Mutations in the gene encoding FYVE and coiled-coil domain containing 1 (FYCO1), a PI(3)P-binding protein family member that is associated with the exterior of autophagosomes and mediates microtubule plus-end-directed vesicle transport, were identified in 12 Pakistani families and one Arab Israeli family in which arCC had previously been mapped to the overlapping CATC2 region. Nine different mutations were identified, including c.3755 delC (p.Ala1252AspfsX71), c.3858_3862dupGGAAT (p.Leu1288TrpfsX37), c.1045 C>T (p.Gln349X), c.2206C>T (p.Gln736X), c.2761C>T (p.Arg921X), c.2830C>T (p.Arg944X), c.3150+1 G>T, c.4127T>C (p.Leu1376Pro), and c.1546C>T (p.Gln516X). Fyco1 is expressed in the mouse embryonic and adult lens and peaks at P12d. Expressed mutant proteins p.Leu1288TrpfsX37 and p.Gln736X are truncated on immunoblots. Wild-type and p.L1376P FYCO1, the only missense mutant identified, migrate at the expected molecular mass. Both wild-type and p. Leu1376Pro FYCO1 proteins expressed in human lens epithelial cells partially colocalize to microtubules and are found adjacent to Golgi, but they primarily colocalize to autophagosomes. Thus, FYCO1 is involved in lens development and transparency in humans, and mutations in this gene are one of the most common causes of arCC in the Pakistani population