Akiko Hikoya

Objective: The objective of this study is to investigate factors associated with outcomes after 3 months of instructed usage of hand-held digital devices (DD) in patients with acquired comitant esotropia (ACE). Methods and analysis: This prospective multicentre observational study included patients with ACE, aged 5–35 years, who used DD within 1 year of onset and were followed up for clinical findings and instructed use of DD. The outcomes were classified into four groups: cured, improved, unchanged and worsened. After the analysis of group differences in the clinical and DD use-related factors by univariate analysis, we used ordinal logistic regression models to identify factors associated with favourable outcomes. Results: Of 156 patients (mean age (SD): 16.4 (7.4) years), 10 (6%), 58 (37%), 67 (43%) and 21 (14%) were classified into the cured, improved, unchanged, and worsened, respectively. In the univariate analysis, consultation within 3 months of onset, small-angle strabismus at distance and good stereoacuity were associated with good outcomes. Ordinal logistic regression analysis on adjusting for age with stereoacuity or successful DD-use time halving showed that small-angle strabismus at distance (OR: 1.02, 95% CI 1.00 to 1.03, p=0.023), good stereoacuity (OR: 1.31; 95% CI 1.10 to 1.56; p=0.003) and successful halving of DD-use time (OR: 0.63; 95% CI 0.43 to 0.92; p=0.016) influenced favourable outcomes. Conclusion: Patients with small-angle esotropia, good stereoacuity on consultation and success in halving DD-use time had a higher chance of recovery through instructional DD usage. Further studies using objectively measurable systems are needed to ensure the accuracy of DD-use time.

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy. RPGRIP1-related LCA accounts for 5–6% of LCA. We performed whole-exome sequencing and whole-genome sequencing (WGS) on 29 patients with clinically suspected LCA and examined ophthalmic findings in patients with biallelic pathogenic variants of RPGRIP1. In addition to five previously reported cases, we identified five cases from four families with compound heterozygous RPGRIP1 variants using WGS. Five patients had null variants comprising frameshift variants, an Alu insertion, and microdeletions. A previously reported 1339 bp deletion involving exon 18 was found in four cases, and the deletion was relatively prevalent in the Japanese population (allele frequency: 0.002). Microdeletions involving exon 1 were detected in four cases. In patients with RPGRIP1 variants, visual acuity remained low, ranging from light perception to 0.2, and showed no correlation with age. In optical coherence tomography images, the ellipsoid zone (EZ) length decreased with age in all but one case of unimpaired EZ. The retinal structure was relatively preserved in all cases; however, there were cases with great differences in visual function compared to their siblings and a 56-year-old patient who still had a faint EZ line. Structural abnormalities may be important genetic causes of RPGRIP1-related retinal dystrophy in Japanese patients, and WGS was useful for detecting them.