[Detection of the spontaneous blinking pattern of dry eye patients using the machine learning method].

Objective: To establish a method to record the spontaneous blink pattern with a machine learning model, and to clarify the spontaneous blink pattern in patients with dry eye. Methods: It was a cross-setional study.We selected 357 dry eye patients (102 males and 255 females), aged (46.2±13.3) years, who visited corneal specialist clinics of Beijing Tongren Eye Center in 2019, as the dry eye group. The control group enrolled 152 normal controls, including 32 males and 120 females, aged (48.1±13.9) years. All participants completed the Ocular Surface Disease Index questionnaire, blink video capture, lipid layer thickness measurement, tear break-up time measurement, corneal fluorescein staining, and Schirmer Ⅱ test. Based on the assembled model built using UNet image segmentation algorithm and ResNet image classification algorithm, single frames of the blink video were analyzed, and then the palpebral opening height of each frame was obtained in order to establish a spontaneous blink wave. Finally, the characteristics of spontaneous blinks in dry eye patients were analyzed based on different types of complete blinks (types A, B and C) and partial blinks (types Ⅰ, Ⅱ and Ⅲ). Independent sample t test and Wilcoxon rank-sum test were used to judge if there was significant difference between the dry eye group and the normal group. Results: The accuracy of the segmentation model and the classification model was 96.3% and 96.0%, respectively, and the consistency with the manual analysis was 97.9%. In dry eye patients, the number of blinks was 30 (18, 42)/min, which was higher than that in normal controls [20 (9, 46)/min] (U=18 132.50, P=0.002). The number of complete blinks in dry eye cases was significantly lower than that in normal controls [6 (3, 24)/min vs. 12 (3,33)/min; U=12 361.00, P=0.016], and the number of partial blinks was significantly higher than that in normal controls [15 (6, 27)/min vs. 3 (0, 10)/min; U=22 839.00, P<0.001]. In complete blinks, the proportion of type A blinks in dry eye patients was significantly higher than that in normal controls [53.7% (2 796/5 177) vs. 39.3% (633/1 698); χ²=101.83, P<0.001]; in partial blinks, the proportion of type Ⅱ blinks in dry eye patients was significantly higher than that in normal controls [36.0%(2 334/6 477) vs. 29.6%(126/426); χ²=6.99, P=0.007]. The average interblink interval of dry eye patients was 1.2 s, which was not significantly different from that of normal controls (1.1 s; U=15 230.00, P=0.093). The eyelid closed phase of dry eye patients was 0.8 s, which was significantly shorter than that of normal controls (1.3 s; U=16 291.50, P=0.006). There were no significant differences in eyelid closing phase, early opening phase and late opening phase between the two groups (all P>0.05). Conclusions: In dry eye patients, the number of partial blinks increased, the number of complete blinks decreased, and the duration of eyelid closed phase shortened significantly. The main blink patterns of dry eye patients included type Ⅱ partial blinks with a reduced closure amplitude and type A complete blinks with a shortened closure time.

[Intellectual developmental disorder with cardiac arrhythmia syndrome in a family caused by GNB5 variation and literature review].

Objective: To explore the clinical characteristics of intellectual developmental disorder with cardiac arrhythmia syndrome (IDDCA) in a family caused by GNB5 gene variation and to review the literature. Methods: The clinical and genetic data of an infant with IDDCA, who visited Shenzhen Children's Hospital in September 2018, were collected and analyzed. His parents' and brother's gene analysis was also done by the next-generation sequencing and confirmed by Sanger sequencing. Related literature up to March 2020 was searched in Online Mendelian Inheritance in Man (OMIM), PubMed, CNKI and Wanfang databases with "GNB5" "IDDCA" "LADCI" "intellectual developmental disorder with cardial arrhythmia" "language delay and attention deficit-hyperactivity disorder or cognitive impairment with or without cardiac arrhythmia" as the key words. The related papers were retrieved and analyzed to summarize the clinical and genetic characteristics of this disorder. Results: The proband was an 11-month-old boy who presented with mental and motor developmental retardation, accompanied with convulsion and muscle weakness. Sinus arrest was also detected. His electroencephalogram (EEG) and flash visual evoked potential (FVEP) were both abnormal. Genetic analysis identified the homozygous frameshift variation of GNB5 gene (c.136delG, p.Glu46Argfs*8) in this infant and heterozygous variation in his parents, confirmed the diagnosis of IDDCA. The same GNB5 variation was identified in his brother, who was 4 years and 8 months old and had developed the similar clinical manifestations after birth. There were only 7 papers reporting this disease in the literature review, with a total of 27 patients from 14 families. Including these 2 cases, there were 29 patients in total, whose age of diagnosis ranged from 5.5 months to 23 years. Among all the patients, 20 cases (69%) were diagnosed as IDDCA, while 8 cases (28%) as LADCI; and 11 (38%) were males while 18 (62%) females. Regarding the clinical features, 66% (19/29) had mental retardation, 41% (12/29) had seizures, 79% (23/29) developed language delay and 62%（18/29） had sinus node dysfunction. Genetic tests showed that 4 patients from 3 families had complex heterozygous variation, and 25 patients (86%) from 12 families had homozygous variation. Seventeen patients from 8 families were consanguineous. Among the total 12 variations, there were 4 nonsense, 3 frameshift, 2 missense and 2 shear mutations, and 1 shear disorder caused by synonymous mutation. Conclusions: IDDCA caused by GNB5 gene variations mainly manifests as general developmental delay or severe mental retardation, and sinus node dysfunction. GNB5 associated syndromes have phenotypic heterogeneity and are inherited in an autosomal recessive manner.