Relationships among Clinical Factors and Patient-reported Outcome Measures in Adults with Convergence Insufficiency.

SIGNIFICANCE: When exploring relationships among clinical measures and patient-reported outcome measures in adults with convergence insufficiency, worse symptoms (Convergence Insufficiency Symptom Survey [CISS] score) seemed to be correlated with worse reading function domain score (Adult Strabismus-20 quality-of-life questionnaire). After treatment, improved symptoms were associated with improved reading function quality of life. PURPOSE: This study aimed to explore relationships between clinical measures and patient-reported outcome measures in adults undergoing treatment for symptomatic convergence insufficiency. METHODS: In a prospective multicenter observational study, we evaluated adults with symptomatic convergence insufficiency (i.e., clinical measures of near exodeviation, receded near point of convergence, reduced near positive fusional vergence; CISS score ≥21). Fifty-seven participants treated with vision therapy/exercises (n = 35) or base-in prism (n = 22) were analyzed. Spearman correlation coefficients ( R ) were used to assess associations among the three clinical measures and patient-reported outcome measures (CISS, Diplopia Questionnaire, four Adult Strabismus-20 quality-of-life domains) before treatment (baseline) and after 10 weeks and 1 year. Associations were interpreted to be present when the lower limit of the 95% confidence interval (CI) was moderate to strong ( R ≥ 0.4). RESULTS: Among multiple exploratory analyses, the only moderate to strong baseline correlation was between worse CISS and worse Adult Strabismus-20 reading function scores ( R = 0.62; 95% CI, 0.43 to 0.76). Regarding change in measures with treatment, the only moderate to strong correlations were between improved CISS and improved Adult Strabismus-20 reading function scores for prism at 10 weeks ( R = 0.78; 95% CI, 0.52 to 0.91) and 1 year ( R = 0.85; 95% CI, 0.65 to 0.94) and for vision therapy/exercises at 1 year ( R = 0.78; 95% CI, 0.57 to 0.89). CONCLUSIONS: In exploratory analyses, we found positive correlations between CISS symptom scores and reading function quality-of-life scores. The absence of correlations between symptoms and individual clinical measures is consistent with clinical experience that, in convergence insufficiency, symptoms and clinical findings can be discordant.

Conserved Asf1-importin ß physical interaction in growth and sexual development in the ciliate Tetrahymena thermophila.

How the eukaryotic cell specifies distinct chromatin domains is a central problem in molecular biology. The ciliate protozoan Tetrahymena thermophila features a separation of structurally and functionally distinct germ-line and somatic chromatin into two distinct nuclei, the micronucleus (MIC) and macronucleus (MAC) respectively. To address questions about how distinct chromatin states are assembled in the MAC and MIC, we have initiated studies to define protein-protein interactions for T. thermophila chromatin-related proteins. Affinity purification followed by mass spectrometry analysis of the conserved Asf1 histone chaperone in T. thermophila revealed that it forms a complex with an importin ß, ImpB6. Furthermore, these proteins co-localized to both the MAC and MIC in growth and development. We suggest that newly synthesized histones H3 and H4 in T. thermophila are transported via Asf1-ImpB6 in an evolutionarily conserved pathway to both nuclei where they then enter nucleus-specific chromatin assembly pathways. These studies set the stage for further use of functional proteomics to elucidate details of the characterization and functional analysis of the unique chromatin domains in T. thermophila. BIOLOGICAL SIGNIFICANCE: Asf1 is an evolutionarily conserved chaperone of H3 and H4 histones that functions in replication dependent and independent chromatin assembly. Although Asf1 has been well studied in humans and yeast (members of the Opisthokonta lineage of eukaryotes), questions remain concerning its mechanism of function. To obtain additional insight into the Asf1 function we have initiated a proteomic analysis in the ciliate protozoan T. thermophila, a member of the Alveolata lineage of eukaryotes. Our results suggest that an evolutionarily conserved function of Asf1 is mediating the nuclear transport of newly synthesized histones H3 and H4.