Nomogram to predict severe retinopathy of prematurity in Southeast China.

AIM: To define the predictive factors of severe retinopathy of prematurity (ROP) and develop a nomogram for predicting severe ROP in southeast China. METHODS: Totally 554 infants diagnosed with ROP hospitalized in the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University and hospitalized in Taizhou Women and Children's Hospital were included. Clinical data and 43 candidate predictive factors of ROP infants were collected retrospectively. Logistic regression model was used to identify predictive factors of severe ROP and to propose a nomogram for individual risk prediction, which was compared with WINROP model and Digirop-Birth model. RESULTS: Infants from the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (n=478) were randomly allocated into training (n=402) and internal validation group (n=76). Infants from Taizhou Women and Children's Hospital were set as external validation group (n=76). Severe ROP were found in 52 of 402 infants, 12 of 76 infants, and 7 of 76 infants in training group, internal validation group, and external validation group, respectively. Birth weight [odds ratio (OR), 0.997; 95% confidence interval (CI), 0.996-0.999; P<0.001], multiple births (OR, 1.885; 95%CI, 1.013-3.506; P=0.045), and non-invasive ventilation (OR, 0.288; 95%CI, 0.146-0.570; P<0.001) were identified as predictive factors for the prediction of severe ROP, by univariate analysis and multivariate analysis. For predicting severe ROP based on the internal validation group, the areas under receiver operating characteristic curve (AUC) was 78.1 (95%CI, 64.2-92.0) for the nomogram, 32.9 (95%CI, 15.3-50.5) for WINROP model, 70.2 (95%CI, 55.8-84.6) for Digirop-Birth model. In external validation group, AUC of the nomogram was also higher than that of WINROP model and Digirop-Birth model (80.2 versus 51.1 and 63.4). The decision curve analysis of the nomogram demonstrated better clinical efficacy than that of WINROP model and Digirop-Birth model. The calibration curves demonstrated a good consistency between the actual severe ROP incidence and the predicted probability. CONCLUSION: Birth weight, multiple births, and non-invasive ventilation are independent predictors of severe ROP. The nomogram has a good ability to predict severe ROP and performed well on internal validation and external validation in southeast China.

Phenotypic variability of SLC7A14 mutations in patients with inherited retinal dystrophy.

BACKGROUND: Inherited retinal dystrophy (IRD) is a group of retinal disorders that are both clinically and genetically diverse, typically with loss of photoreceptor function. Herein, we aimed to identify the underlying genetic defect in IRD patients with mutations in the SLC7A14 gene. METHODS: A targeted exome capture panel was applied for mutational screening of SLC7A14. Targeted exome sequencing (TES) was performed on 200 non-syndromic and unrelated autosomal recessive or sporadic IRD families. Candidate variants were validated by direct sequencing and further examined using bioinformatics analyses for determination of their potential effect. RESULTS: We identified compound heterozygous missense mutations (c.988G>A, p.G330R; c.1970G>A, p.R657Q) in an autosomal recessive retinitis pigmentosa (RP) case and a homozygous mutation (c.988G>A, p.G330R) in a simplex case with Leber congenital amaurosis (LCA) in the SLC7A14 gene. Both G330R and R657Q were deleterious based on in silico predictive tools. Our proposed topological model of the SLC7A14 polypeptide suggested that both G330R and R657Q affected evolutionarily highly conserved amino acid residues in SLC7A14 that occurred in transmembrane helixes. Structural modeling revealed a broken arginine and aspartic acid connection between residues 657 and 406. CONCLUSIONS: We applied TES to the molecular diagnosis of patients with IRD and for the first time identified SLC7A14 mutations in two unrelated families with RP and LCA separately. Our findings uniquely add the knowledge of the phenotypic variability of SLC7A14 mutations.

Whole-exome sequencing identifies USH2A mutations in a pseudo-dominant Usher syndrome family.

Usher syndrome (USH) is an autosomal recessive (AR) multi-sensory degenerative disorder leading to deaf-blindness. USH is clinically subdivided into three subclasses, and 10 genes have been identified thus far. Clinical and genetic heterogeneities in USH make a precise diagnosis difficult. A dominant­like USH family in successive generations was identified, and the present study aimed to determine the genetic predisposition of this family. Whole­exome sequencing was performed in two affected patients and an unaffected relative. Systematic data were analyzed by bioinformatic analysis to remove the candidate mutations via step­wise filtering. Direct Sanger sequencing and co­segregation analysis were performed in the pedigree. One novel and two known mutations in the USH2A gene were identified, and were further confirmed by direct sequencing and co­segregation analysis. The affected mother carried compound mutations in the USH2A gene, while the unaffected father carried a heterozygous mutation. The present study demonstrates that whole­exome sequencing is a robust approach for the molecular diagnosis of disorders with high levels of genetic heterogeneity.

[Magnetic resonance imaging study of effects of accommodation on human lens morphological characters].

OBJECTIVE: To evaluate the effects of accommodation on lens morphological characters. METHODS: From January 2011 to June 2011, magnetic resonance images of eyes were acquired from 30 subjects aged 20 to 24 years during accommodation and at rest. The optimal images were analyzed by Autocad 2010 to obtain the total lens cross-sectional area (CSA) and CSA of anterior and posterior portions of lens, anterior chamber depth, lens thickness, lens diameter, vitreous chamber depth and axial length during accommodation and at rest. Paired-t test was performed. RESULTS: The anterior curvature radius (mm), posterior curvature radius (mm), CSA of anterior portion (mm(2)), CSA of posterior portion (mm(2)), total lens CSA (mm(2)) was (8.7 ± 0.8), (6.2 ± 0.5), (7.5 ± 2.1), (12.0 ± 2.6), (20 ± 4) during relaxed accommodation; anterior curvature radius (mm), posterior curvature radius (mm), CSA of anterior portion (mm(2)), CSA of posterior portion (mm(2)), total lens CSA (mm(2)) was (7.1 ± 1.3), (5.6 ± 0.5), (14.7 ± 2.9), (12.2 ± 2.1) and (27 ± 4) during accommodation. The total lens CSA (t = -11.556, P < 0.01) and CSA of anterior portion (t = -15.653, P < 0.01) both increased in accommodative states. The CSA of posterior portion of lens (t = -0.437, P > 0.05) under a statistically independent accommodative state. There was significant difference in the anterior chamber depth (t = 4.366, P < 0.01), lens thickness (t = -5.456, P < 0.01) and lens diameter (t = 4.597, P < 0.01) in accommodative states. There were insignificant differences both in vitreous chamber depth (t = 0.428, P > 0.05) and axial length (t = 0.418, P > 0.05) under accommodative states. CONCLUSION: During accommodation, the anterior chamber depth decreases, lens thickness increases and diameter of lens decreases while anterior portions and total lens CSA increase. There are insignificant changes in posterior portions of lens CSA, vitreous chamber depth and axial length. The accommodative changes in CSA indicate that the anterior portion of lens may be related with the properties of anterior capsule and lens material, the position of zonular attachments and the location of fetal nucleus. Helmholtz theory is supported.

[Macular and retinal nerve fiber layer thickness in myopic children by three-dimensional OCT].

OBJECTIVE: To investigate the variations of macular thickness and peripapillary retinal nerve fiber layer (RNFL) thickness in myopic children. METHODS: A total of 96 eyes from 48 myopic children at department of Ophthalmology, Second Affiliated Hospital of Wenzhou Medical College from September 2010 to March 2012 were enrolled in this study and divided into three groups (low, moderate and high myopia group) according to the severity of myopia. Another 33 eyes from 19 emmetropic children were recruited as control group. The macular thickness and peripapillary RNFL thickness of the myopic children measured by optical coherence tomography were compared with that of the control group. RESULTS: The mean thickness of nasal, superior and inferior regions of outer-ring macular in the high myopia group were 276 µm, 294 µm, 285 µm respectively, which were significantly lower than that in the control group (P < 0.05). The mean thickness of superior of outer-ring macular in the low and moderate groups were 302 µm, 301 µm respectively, and the inferior of outer-ring ones were 288 µm, 283 µm respectively, which were significantly lower than that in the control group (P < 0.05). The temporal region of peripapillary RNFL thickness was significantly greater, and the other six regions of RNFL thicknesses were significantly lower in the high group than in the control group (P < 0.05). The central-1 mm, superior region of inner-ring, temporal and superior region of outer-ring macular thickness had positive correlations with spherical equivalent (SE) (P < 0.05). There was a negative correlation between the temporal peripapillary RNFL thickness and SE, while positive correlations were found between other regions of peripapillary RNFL thickness and SE (P < 0.05). CONCLUSIONS: The thicknesses of macular and peripapillary RNFL of myopic children have already redistributed before apparent changes of funds.

[Studies of genetic polymorphism in retinopathy of prematurity].

Retinopathy of prematurity (ROP) is a vasoproliferative disease that happened in preterm infants with low gestational age and birth weight. Recently, many studies suggested that the incidence of ROP and the results of same clinical intervention vary between different races and countries. It seems that ROP may relate with genetic factors. Several genes are suggested to play a possible role in the occurrence of ROP. This paper reviews these related genes.