Euthyroid graves' ophthalmopathy in a Chinese population: A cross-sectional follow-up study.

OBJECTIVES: A subtype of patients with thyroid eye disease (TED) were found to be euthyroid without prior thyroid dysfunction or treatment, known as Euthyroid Graves' Ophthalmopathy (EGO). We report the prevalence, clinical and serological phenotypes of EGO in a Chinese population. METHODS: A cross-sectional follow-up study. Ethnic Chinese TED patients were managed at the Thyroid Eye Clinic(TEC), Prince of Wales Hospital and TEC, the Chinese University of Hong Kong between September 2007 and July 2021. RESULTS: A total of 66 (5%) patients among the 1266 ethnic Han Chinese TED cohort were diagnosed as EGO, and 6 (9%)of them become dysthyroid over an average of 74-month follow-up. EGO patients were associated with a longer duration between onset of the symptoms to our first consultation (P < 0.0001), a higher male-to-female ratio (P = 0.0045) and a higher age of disease onset (P = 0.0092). Family history of thyroid disease was more common in TED patients (P = 0.0216) than in EGO patients. EGO patients were more likely to present unilaterally (P < 0.0001), and they have a larger difference in MRD1 (P < 0.0001), and extraocular motility (P < 0.0001) between the 2 eyes when compared to the TED patients. Notably, the extraocular motility restriction of the worst eye was more affected in EGO patients (P = 0.0113). The percentages of patients who received IVMP, ORT and emergency or elective surgeries(decompression or squint operation) between EGO and TED were similar. CONCLUSIONS: Understanding the important clinical phenotypes of EGO may help the clinician to make the correct diagnosis. Further study to compare EGO and TED is warranted.

Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children.

PURPOSE: Association of SIX1-SIX6 variants with peripapillary retinal nerve fibre layer (p-RNFL) thickness had been reported in adults. This study aimed to investigate these associations in children, with further explorations by spatial, age and sex stratifications. METHODS: 2878 school children aged between 6 and 9 years were enrolled from the Hong Kong Children Eye Study. Three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6 locus were genotyped. The association of each SNP with p-RNFL thickness (including global and sectoral thickness) were evaluated using multiple linear regression. RESULTS: SNPs rs33912345 (p=7.7×10-4) and rs10483727 (p=0.0013) showed significant associations with temporal-inferior p-RNFL thickness. The C allele of rs33912345 was associated with a thinner temporal-inferior p-RNFL by an average of 2.44 µm, while rs10483727-T was associated with a thinner temporal-inferior p-RNFL by 2.32 µm. The association with temporal-inferior p-RNFL was the strongest in the 8-9 year-old group for rs33912345 (p=5.2×10-4) and rs10483727 (p=3.3×10-4). Both SNPs were significantly associated with temporal-inferior p-RNFL thickness in boys (p<0.0017), but not in girls (p>0.05). In contrast, rs12436579-C (ß=1.66; p=0.0059), but not rs33912345-C (ß=1.31; p=0.052) or rs10483727-T (ß=1.19; p=0.078), was nominally associated with a thicker nasal-inferior p-RNFL. CONCLUSIONS: Both rs33912345 and rs10483727 at SIX1-SIX6 were associated with p-RNFL thickness in children, especially at the temporal-inferior sector, with age-dependent and sex-specific effects. SNP rs12436579 was associated with nasal-inferior p-RNFL thickness. Our findings suggested a role of SIX1-SIX6 in RNFL variation during neural retina development in childhood.

Association of polymorphisms in ZFHX1B, KCNQ5 and GJD2 with myopia progression and polygenic risk prediction in children.

AIMS: To assess the association of single-nucleotide polymorphisms (SNPs) with myopia progression for polygenic risk prediction in children. METHODS: Six SNPs (ZC3H11B rs4373767, ZFHX1B rs13382811, KCNQ5 rs7744813, MET rs2073560, SNTB1 rs7839488 and GJD2 rs524952) were analysed in 1043 school children, who completed 3-year follow-up, using TaqMan genotyping assays. SNP associations with progression in spherical equivalent (SE) were analysed by logistic regression. Polygenic risk scores (PRS) were applied for computing the sum of the risk alleles of multiple SNPs corresponding to myopia progression, weighted by the effect sizes of corresponding SNPs. RESULTS: GJD2 rs524952 showed significant association with fast progression (OR=1.32, 95% CI 1.10 to 1.59; p=0.003) and KCNQ5 rs7744813 had nominal association (OR=1.32, 95% CI 1.04 to 1.67; p=0.02). In quantitative traits locus analysis, GJD2 rs524952 and KCNQ5 rs7744813 were associated with progression in SE (ß=-0.038 D/year, p=0.008 and ß=-0.042 D/year, p=0.02) and axial elongation (ß=0.016 mm/year, p=0.01 and ß=0.017 mm/year, p=0.027). ZFHX1B rs13382811 also showed nominal association with faster progression in SE (ß=-0.041 D/year, p=0.02). PRS analysis showed that children with the highest PRS defined by rs13382811, rs7744813 and rs524952 had a 2.26-fold of increased risk of fast myopia progression (p=4.61×10-5). PRS was also significantly associated with SE progression (R2=1.6%, p=3.15×10-5) and axial elongation (R2=1.2%, p=2.6×10-4). CONCLUSIONS: In this study, multi-tiered evidence suggested SNPs in ZFHX1B, KCNQ5 and GJD2 as risk factors for myopia progression in children. Additional attention and appropriate interventions should be given for myopic children with high-risk PRS as defined by GJD2 rs524952, KCNQ5 rs7744813 and ZFHX1B rs13382811.