Magnetic Resonance Imaging Findings in Patients With Duane Retraction Syndrome.

BACKGROUND: Duane retraction syndrome (DRS) is known to relate to the absence of the abducens nucleus, with abnormal innervation of the lateral rectus (LR) muscle by branchesof the oculomotor nerve (CN III). The purposes of this study were to investigate the morphological characteristics of the oculomotor nerve (CN III), the abducens nerve (CN VI), and the extraocular muscles in patients with clinically diagnosed Duane retraction syndrome (DRS) using MRI. In addition, we assessed the association between ocular motility, horizontal rectus muscle volumes, and CN III/VI in patients with Duane retraction syndrome (DRS). METHODS: The study comprised 20 orthotropic control subjects (40 eyes) and 42 patients with Duane syndrome (48 eyes), including 20 patients with DRS Type I (24 eyes), 5 patients with DRS Type II (6 eyes), and 17 patients with DRS Type III (18 eyes). Three-dimensional (3D) T1/2 images of the brainstem and orbit were obtained to visualize the cranial nerves, especially the abducens (VI) and oculomotor (III) nerves, as well as extraocular muscles. RESULTS: Based on the clinical classification, among 42 patients, MRI showed that the abducens nerves (CN VI) on the affected side were absent in 24 of 24 eyes (100%; 20 patients) with Type I DRS and in 16 of 18 eyes (88%; 16 patients) with Type III DRS. However, CN VI was observed in 6 of 6 eyes (100%; 5 patients) with Type II DRS and in 2 of 18 eyes (11%) with Type III DRS. CN III was observed in all patients. The oculomotor nerves on the affected side were thicker than those on the nonaffected contralateral side in DRS Type I ( P < 0.05) and Type III ( P < 0.05), but not in DRS Type II. Smaller LR and larger MR volumes were shown in the affected eye than that in the nonaffected eye in DRS Types I and III. Based on the presence or absence of CN VI, there was a tendency for thicker oculomotor nerves in the affected eye than in the nonaffected eye in the absence groups ( P < 0.05). However, no significant difference was found in the present group. In the CN VI absence groups, similar results were found in the affected eyes than in the nonaffected eyes as in DRS Types I and III. In addition, the presence of CN VI was correlated with better abduction ( P = 0.008). The LR and MR volumes have positive correlations with the oculomotor nerve diameter in the affected eye. However, there was no correlation between the range of adduction/abduction and the LR/MR ratio in patients with or without an abducens nerve. CONCLUSIONS: Different types of DRS have different characteristic appearances of CN VI and CN III on MRI. Horizontal rectus muscles have morphological changes to adapt to dysinnervation of CN VI and aberrant innervation of CN III. Thus, these neuroimaging findings may provide a new diagnostic criterion for the classification of DRS, improving the comprehension of the physiopathogenics of this disease.

PRPF4 mutations cause autosomal dominant retinitis pigmentosa.

Retinitis pigmentosa (RP), a disease characterized by progressive loss of photoreceptors, exhibits significant genetic heterogeneity. Several genes associated with U4/U6-U5 triple small nuclear ribonucleoprotein (tri-snRNP) complex of the spliceosome have been implicated in autosomal dominant RP (adRP). HPrp4, encoded by PRPF4, regulates the stability of U4/U6 di-snRNP, which is essential for continuous splicing. Here, we identified two heterozygous variants in PRPF4, including c.-114_-97del in a simplex RP patient and c.C944T (p.Pro315Leu), which co-segregates with disease phenotype in a family with adRP. Both variants were absent in 400 unrelated controls. The c.-114_-97del, predicted to affect two transcription factor binding sites, was shown to down-regulate the promoter activity of PRPF4 by a luciferase assay, and was associated with a significant reduction of PRPF4 expression in the blood cells of the patient. In fibroblasts from an affected individual with the p.Pro315Leu variant, the expression levels of several tri-snRNP components, including PRPF4 itself, were up-regulated, with altered expression pattern of SC35, a spliceosome marker. The same alterations were also observed in cells over expressing hPrp4(Pro315Leu), suggesting that they arose as a compensatory response to a compromised splicing mechanism caused by hPrp4 dysfunction. Further, over expression of hPrp4(Pro315Leu), but not hPrp4(WT), triggered systemic deformities in wild-type zebrafish embryos with the retina primarily affected, and dramatically augmented death rates in morphant embryos, in which orthologous zebrafish prpf4 gene was silenced. We conclude that mutations of PRPF4 cause RP via haploinsufficiency and dominant-negative effects, and establish PRPF4 as a new U4/U6-U5 snRNP component associated with adRP.

[Apply of RetCam â ¡ and color Doppler imaging in persistent hyperplastic primary vitreous].

OBJECTIVE: To observe the manifestations of RetCam Ⅱ and color Doppler imaging (CDI) in a retrospective case series of persistent hyperplastic primary vitreous (PHPV). METHODS: Retrospective study. The medical records of 9 eyes/9 patients with PHPV went through RetCamⅡ and CDI from 2009 to 2014. RESULTS: There were 6 young boys and 3 young girl in this study, age from 2 months to 5 years. All the patients were born at full term. 9 eyes had complication (cataract). The manifestations of RetCam Ⅱ: There were pale in optic disc. There were white fibre rod connected with optic disc, then prolonged to vitreous cavity, connected with posterior lens capsule. CDI showed arterial blood stream signal in band-shaped echogenic structure within vitreous cavity, prolonged to lens from the optic disc, or showed funnel-shaped echogenic mass at the posterior surface of lens and anterior of vitreous body, adhered to ciliary body, lens and the optic disc. CONCLUSIONS: PHPV is congenital ocular anomalies because of a failure of primary vitreous and the hyaloids vascular system to regress. It manifests as unilateral and boys. We diagnosis PHPV by RetCamⅡ and CDI.

[Hot topics in treatment of intermittent exotropia].

Intermittent exotropia is the most common type of exotropia, and also is one of the most difficult types of strabismus to deal with. Surgery is the main choice of treatment and non-surgical treatment is used only under certain indications. Long-term outcomes of the surgery for intermittent exotropia are related to many factors, such as age, course of the disease, perceptual state of visual cortex, timing of surgery, types of intermittent exotropia, the surgical methods, preoperative measurements of exodeviations, target angle of surgery, postoperative treatment of overcorrection or undercorrection, and so on. It is significant to pay attention to these issues to improve success rate of the surgeries. In this paper, recent progress of clinical studies of intermittent exotropia were reviewed to arouse the attentions of domestic ophthalmologist to the standardization of diagnosis and treatment of intermittent exotropia.

[The developmental switch of visual cortex NMDA receptor NR2 subunits and its implications for visual plasticity].

Many forms of synaptic plasticity require NMDA-type glutamate receptors (NMDAR). These tetrameric receptors consist of two obligatory NR1 subunits and two regulatory subunits, usually a combination of NR2A and NR2B. In the neonatal visual cortex NR2B-containing NMDAR predominate, after thatvisual experience facilitates a developmental switch in which NR2A levels increase relative to NR2B. In this review, it puts emphasis on the role and the regulation of this shift as well as the effect on synaptic plasticity.

[See the strabismus and amblyopia research development trend from the twelfth World Congress of strabismus].

The International strabismus association conference has a history of fifty years until now. It's the most influential academic communication forum for the worldwide doctors and related scientists or technical carers in strabismus and amblyopia area. The conference gathered the top-level experts. The latest clinical/research achievements of strabismus, amblyopia in the field of binocular vision and ocular motility have been showed. The breakthroughs in the etiology study of incomitant strabismus have been and are being transformed into new therapeutic concepts and techniques. Re-adjust the competition between dominant and amblyopic eye using binocular stimulation methods may overcome the existing defects of monocular occlusion therapy, expand new interventional methods to treat amblyopia, and represent the future trends of amblyopia therapy. In this paper, we will introduce the main contents of the XII ISA meeting and spread knowledge of strabismus/amblyopia promoting directions in order to provide reference ideas for the clinicians and research colleagues in this field.

Mutation analysis of pre-mRNA splicing genes in Chinese families with retinitis pigmentosa.

PURPOSE: Seven genes involved in precursor mRNA (pre-mRNA) splicing have been implicated in autosomal dominant retinitis pigmentosa (adRP). We sought to detect mutations in all seven genes in Chinese families with RP, to characterize the relevant phenotypes, and to evaluate the prevalence of mutations in splicing genes in patients with adRP. METHODS: Six unrelated families from our adRP cohort (42 families) and two additional families with RP with uncertain inheritance mode were clinically characterized in the present study. Targeted sequence capture with next-generation massively parallel sequencing (NGS) was performed to screen mutations in 189 genes including all seven pre-mRNA splicing genes associated with adRP. Variants detected with NGS were filtered with bioinformatics analyses, validated with Sanger sequencing, and prioritized with pathogenicity analysis. RESULTS: Mutations in pre-mRNA splicing genes were identified in three individual families including one novel frameshift mutation in PRPF31 (p.Leu366fs*1) and two known mutations in SNRNP200 (p.Arg681His and p.Ser1087Leu). The patients carrying SNRNP200 p.R681H showed rapid disease progression, and the family carrying p.S1087L presented earlier onset ages and more severe phenotypes compared to another previously reported family with p.S1087L. In five other families, we identified mutations in other RP-related genes, including RP1 p. Ser781* (novel), RP2 p.Gln65* (novel) and p.Ile137del (novel), IMPDH1 p.Asp311Asn (recurrent), and RHO p.Pro347Leu (recurrent). CONCLUSIONS: Mutations in splicing genes identified in the present and our previous study account for 9.5% in our adRP cohort, indicating the important role of pre-mRNA splicing deficiency in the etiology of adRP. Mutations in the same splicing gene, or even the same mutation, could correlate with different phenotypic severities, complicating the genotype-phenotype correlation and clinical prognosis.

Maternal germline mosaicism of kinesin family member 21A (KIF21A) mutation causes complex phenotypes in a Chinese family with congenital fibrosis of the extraocular muscles.

PURPOSE: To identify the causative mutation with its possible origin in a Chinese family with congenital fibrosis of extraocular muscles type 1 (CFEOM1) and to characterize the ocular phenotypes and lesions in the corresponding intracranial nerves. METHODS: Three affected siblings and their asymptomatic parents underwent comprehensive ophthalmic examinations and neuropathologic analysis involving magnetic resonance imaging (MRI). KIF21A, PHOX2A, and TUBB3 genes were sequenced on the leukocyte-derived DNA to detect variants. The disease-linked haplotype was analyzed using four microsatellite markers across the KIF21A locus. RESULTS: All three affected individuals displayed typical CFEOM1. MRI revealed complicated but consistent neuromuscular abnormalities in the two patients examined, including hypoplastic oculomotor nerves, complete absence of bilateral superior rectus muscles, and unilateral absence of the abducens nerve with marked atrophy of the corresponding lateral rectus muscle. A heterozygous hotspot mutation KIF21A c.2860C>T was identified in all patients, but it was absent in both parents. Haplotype analysis of the disease locus showed the likely maternal inheritance of the disease-associated haplotype to all three affected offspring, strongly suggesting maternal germline mosaicism of the mutation. CONCLUSIONS: Germline mosaicism of KIF21A c.2860C>T is likely to cause the high occurrence of this mutation in the population. This information may be useful for genetic counseling. KIF21A mutations can affect the abducens nerve and cause complete absence of the bilateral superior rectus muscles. MRI characterization of new CFEOM1 phenotypes would assist clinical management.

[Learn new version of Preferred Practice Pattern to further standardize the diagnosis and treatment of amblyopia].

The introduction of Preferred Practice Patterns (PPP) into China has given ophthalmologists in China more opportunities to acquaint themselves with international clinical guidelines for eye care, including its developing principles, methods and the application value. It had brought significant effects on the fast improvement of clinical eye care and standardization of diagnosis and treatment of eye diseases in China, and promoted the international academic exchanges. The 2nd Chinese version of PPPs translated by Prof. Jialiang Zhao was officially published in November, 2013. The new version of PPP for amblyopia adopted the newest standard for grading of evidence strength and recommendation assessment, and emphasizes the practicability based on evidence. New explanations of the definition of amblyopia are added according to the recent research progresses in amblyopia. The diagnostic criteria of best visual acuity for bilateral amblyopia at different ages is given with new specifications. Comprehensive and practical suggestions on the examination methods for amblyopia are provided from the qualitative assessment of visual acuity, the choice of eye chart, to the use of cycloplegic agents. In the aspect of the treatment of amblyopia, based on the findings of recent multi-central random controlled clinical trials, not only strong recommendations are provided, but also the insufficiency of evidence supporting for some choices of therapy is pointed out. The necessity of the follow-up evaluation after the cessation of the treatment of amblyopia is emphasized too. In the aspect of the prevention of amblyopia, the new amblyopia PPP points out the importance of the early-period screening of amblyopia, and that the healthcare insurance plans should cover timely screening, treatment, and monitoring for recurrence of amblyopia. This article deciphers the essential contents of the new version of Chinese PPP for amblyopia, and aims to promote the standardization of the diagnosis and treatment of amblyopia with our ophthalmic colleagues in China.

[Advance studies of Slit-Robo signal pathway and its roles in ocular neovascularisation].

The migration and patterning of axons and blood vessels share similar guidance mechanisms. Slits and their Roundabout (Robo) receptors were initially characterized as repulsive guidance cues for neuronal axons and mediate the migration of neuronal precursor cells during neural development. In recent years, the research of Slit/Robo signal pathway on neovascularization has become one of hot topics. This review will focus on the role of Slit/Robo signal pathway in ocular neovascularization to promote the research of Slit/Robo signaling on ophthalmology.

[The spatiotemporal frequency tuning of pattern visual evoked potentials in rats].

OBJECTIVE: To observe the spatiotemporal frequency tuning of pattern visual evoked potentials in Wistar rats. METHODS: Experimental study. 15 Wistar rats of 8 weeks old were used in this study. Recording electrodes were chronically inserted into the skull without piercing the dura at the corresponding sites to the primary visual cortex under anesthesia. Reference electrodes were inserted into the nose bone in the same way. Pattern visual evoked potentials were recorded on the 3(rd), 5(th), 7(th) and 9(th) postoperation days. The visual stimuli were chessboard patterns with spatial frequency of 0.01, 0.02, 0.04 or 0.08 cpd, and temporal frequency of 1, 2, 4 or 6 Hz, respectively. Data were processed and statistically analyzed with Matlab and SPSS. The amplitudes and latencies of pattern visual evoked potentials under different spatial and temporal frequencies, the inter-individual variations and the repeated measurement variations were compared. RESULTS: With the increase of spatial frequencies, the P100 amplitudes of PVEPs were gradually reduced, which were (29.87 ± 10.37) µV (0.01 cpd), (31.92 ± 10.98) µV (0.02 cpd), (28.46 ± 6.18) µV (0.04 cpd) and (20.71 ± 6.54) µV(0.08 cpd), respectively, with significant difference among groups (F = 3.725, P = 0.018), and the P100 latencies of PVEPs were gradually elongated, which were (96.25 ± 12.12) ms (0.01 cpd), (95.73 ± 15.13) ms (0.02 cpd), (101.75 ± 8.11) ms (0.04 cpd) and (125.58 ± 18.32) ms (0.08 cpd), respectively, with significant difference among groups (F = 12.187, P = 0.000) . With the increase of temporal frequencies, the P100 amplitudes of PVEPs were gradually reduced, which were (30.71 ± 8.25) µV (1 Hz), (29.75 ± 4.76) µV (2 Hz), (25.79 ± 8.51) µV (4 Hz) and (19.63 ± 6.00) µV (6 Hz), with significant difference among groups (F = 6.115, P = 0.001), and there was no change of P100 latencies, which were (102.58 ± 16.09) ms (1 Hz), (101.75 ± 10.32) ms (2 Hz), (104.25 ± 12.51) ms (4 Hz) and (102.67 ± 13.59) ms (6 Hz), respectively, with no significant difference among groups (F = 0.074, P = 0.974). The inter-individual variation was the smallest under the spatial frequency of 0.04 cpd and temporal frequency of 2 Hz. The repeated measurement variations showed no significant change under tested conditions. CONCLUSION: Under appropriate stimuli and recording conditions, PVEP can be reliably recorded in Wistar rats. The spatiotemporal frequency tuning of P100 amplitudes of Wistar rats exhibit low-pass selectivity. The spatial frequency affects the P100 latency in Wistar rat, but not so does the temporal frequency.

[Experimental study of glyceraldehyde cross-linking of posterior scleral on FDM in guinea pigs].

OBJECTIVE: The purpose of this study is to observe the effects of glyceraldehyde cross-linking on sclera biomechanical strength and experimental myopia. METHODS: 50 three weeks aged guinea pigs were randomly divided into 5 groups: A, B, C, D, E. Each group had 10 guinea pigs. The right eye was set as the experimental eye, the left eye was used as control. Group A: 7 days mask; Group B: 21 days mask, plus physiological saline retrobulbar injection at mask day 1, 8, 15; Group C: 21 days mask, plus 0.05 mol/L glyceraldehyde retrobulbar injection at mask day 1, 8, 15; Group D: 21 days mask, plus 0.5 mol/L glyceraldehyde retrobulbar injection at mask day 1, 8, 15; Group E: normal control group. Several parameters of 7 guinea pigs of each group were measured before and after deprivation (mask day 7, 14, 21), including ocular axial length, refractive error, ultimate stress (σmax) (MPa), ultimate strain(εmax) (%) and 6% elastic modulus (MPa). The effects of glyceraldehyde on adjacent tissues of the rest 3 guinea pigs were detected by histopathological and immunohistochemical studies. Differences between experiment eyes and contralateral, eyes were compared with paired t test and correlative analysis. RESULTS: The experimental eyes appeared the increase of the the vitreous cavity length, the axial length and myopia after deprivation. In group A, group B and group C, the differences of the length of the vitreous cavity (group A (2.991 ± 0.078) mm, group B (2.961 ± 0.038) mm and group C (2.936 ± 0.021) mm), the axial length(group A (7.263 ± 0.133) mm, group B (7.732 ± 0.099) mm and group C (7.665 ± 0.055) mm) and refractive error (group A (-2.214 ± 2.881) D, group B (-4.525 ± 2.415) D and group C (-1.607 ± 0.866) D) between the experimental eye and the fellow eye was statistically significant (vitreous cavity = 3.234, 4.758, 7.608; Pvitreous cavity = 0.018, 0.002, 0.001; axial = 3.198,, 4.758, 7.608; Paxial = 0.019, 0.002, 0.000; refraction = -7.120, -4.020, -6.334; Prefraction = 0.000, 0.005, 0.001). In group D and group E, there is no difference between deprived eye and control eye about the length of the vitreous chamber as well as axial length (vitreous = 0.542, -0.646; Pvitreous cavity = 0.607, 0.539; axial = 0.542, -0.646; Paxial = 0.607, 0.539). The experimental eye ((-3.921 ± 0.874)D) and the fellow eye ((-3.321 ± 1.205)D) of group D, the difference of diopter was statistically significant (refraction = -3.154, Prefraction = 0.020). At the end of the experiment, the change of diopter of experimental eye of group B, C, D, E was significantly different (F = 61.249, P = 0.000). The difference of diopter change between group B ((8.800 ± 0.616) D), group C ( (7.236 ± 2.198) D), group D ( (6.271 ± 1.112) D) and the normal control group ((0.934 ± 0.158) D) was statistically significant (PB = 0.000, PC = 0.000, PD = 0.000). At the end of the experiment, the ultimate stress and 6% elastic modulus of group B experimental eye was (7.988 ± 3.677) MPa (P = 0.002) and (19.938 ± 4.871) MPa (P = 0.001), decreased 10.06% and 34.17% respectively. On the other hand the ultimate strain was (28.6 ± 3.6) % (P = 0.034), increased 19.17%. After the cross-linking treatment, the ultimate stress and 6% elastic modulus of group C experimental eye was (9.244 ± 0.806) MPa (P = 0.001) and (26.180 ± 4.388) MPa (P = 0.031) , decreased 23.13% and 13.34%, the ultimate strain was (26.2 ± 1.0) % (P = 0.016) , increased 12.93% separately. The ultimate stress of group D experimental eye was (12.476 ± 2.507) MPa (P = 0.580), decreased 5.50%, 6% elastic modulus was (30.446 ± 3.410) MPa (P = 0.314), increased 6.53%, ultimate strain was (23.8 ± 1.8) % (P = 0.253), decreased 4.42% respectively. Ultrastructure examination showed that, decreased scleral thickness with fibers lined up in order, without inflammatory cells Infiltration. Expressions of matrix metalloproteinases-2(MMP-2) mainly decrease in the episcleral tissue. The stroma of choroid, and the outer plexiform layer. CONCLUSIONS: Glyceraldehyde is a safe and effective cross-linking agent that could significantly enhance the sclera biomechanical strength. Glyceraldehyde cross-linking method could effectively control the development of myopia in animal model.

[Clinical investigation on AC/A ratio in intermittent exotropia coexisting with ametropia].

OBJECTIVE: To investigate AC/A ratio and coexisting ametropia in intermittent exotropia. To discuss the relation between AC/A ratio and the development of intermittent exotropia. METHODS: The medical records of 135 patients who had an exotropia were retrospectively reviewed. Patients were divided into 3 groups based on the type of ametropia: exotropia without ametropia (-0.50-+3.00 D between the age of 3-6 years old, -0.50-+2.00 D between the age of 7-40 years old) , exotropia coexisting with myopia (-0.50-7.75 D) and exotropia coexisting with hypermetropia ( ≥ + 3.00 D of 3-6 years old , ≥ + 2.00 D of 7 ∼ 40 years old). AC/A ratios of all patients were assessed using synoptophore method. Distance and near deviations were assessed using prism cover test. AC/A ratios and deviation angles of 3 groups were compared. The relationship between AC/A ratios and ametropia/age were investigated. RESULTS: There were obvious differences in AC/A ratios(2.686 ± 1.372, 1.773 ± 1.110, 4.581 ± 1.552, F = 36.323, P < 0.001) and in near deviation angles (44.473(Δ) ± 19.008(Δ), 53.621(Δ) ± 20.749(Δ), 34.455(Δ) ± 13.292(Δ), F = 8.762, P = < 0.001) between 3 groups of patients, no obvious differences were seen in distance deviation angles (40.333(Δ) ± 19.474(Δ), 44.052(Δ) ± 23.722(Δ), 35.590(Δ) ± 11.143(Δ), F = 1.444, P = 0.24). AC/A ratios were negative linear correlated with refractive powers for patients of intermittent extropia coexisting with myopia or with hypermetropia (r = 0.320, P = -0.469 and r = -0.046, P = 0.036, respectively) . A trend of decline with age was found for AC/A ratios only in patients of intermittent extropia without ametropia (r = -0.320, P = 0.019; r = -0.023, P = 0.865; r = 0.246, P = 0.296 for the other 2 groups, respectively). CONCLUSIONS: Myopia and hypermetropia, when coexisting with abnormally low or high AC/A ratio, can destroy the balance between extraocular muscles and induce exophoria to be manifest.

Dark exposure extends the integration window for spike-timing-dependent plasticity.

Metaplasticity, the adaptive changes of long-term potentiation (LTP) and long-term depression (LTD) in response to fluctuations in neural activity is well documented in visual cortex, where dark rearing shifts the frequency threshold for the induction of LTP and LTD. Here we studied metaplasticity affecting spike-timing-dependent plasticity, in which the polarity of plasticity is determined not by the stimulation frequency, but by the temporal relationship between near-coincidental presynaptic and postsynaptic firing. We found that in mouse visual cortex the same regime of deprivation that restricts the frequency range for inducing rate-dependent LTD extends the integration window for inducing timing-dependent LTD, enabling LTD induction with random presynaptic and postsynaptic firing. Notably, the underlying mechanism for the changes in both rate-dependent and time-dependent LTD appears to be an increase of NR2b-containing NMDAR at the synapse. Thus, the rules of metaplasticity might manifest in opposite directions, depending on the plasticity-induction paradigms.

Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis.

BACKGROUND: Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1) is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes. METHODS: Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. RESULTS: Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52). In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77). When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00). We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57). CONCLUSIONS: The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of diabetes (more than 10 years) indicated a gene-environment interaction in determining the risk of diabetic retinopathy.

Two novel mutations of fibrillin-1 gene correlate with different phenotypes of Marfan syndrome in Chinese families.

PURPOSE: To identify the causative mutations in two Chinese families with autosomal dominant Marfan syndrome and to describe the associated phenotypes. METHODS: Complete physical, ophthalmic, and cardiovascular examinations were given to the patients and unaffected individuals in the two families. Exclusive linkage mapping was performed for transforming growth factor beta receptor II (TGFBR2) and fibrillin-1 (FBN1) loci in both families. The entire coding region and flanking splice sites of the FBN1 gene were screened for mutations in the two families with Sanger sequencing. The potential mutations of FBN1 were tested in 100 normal controls. RESULTS: Lens dislocation was observed in two out of ten patients in the MF1 family and all patients in the MF2 family. However, the MF1 family displayed more severe cardiovascular and skeletal system involvement compared with the MF2 family. The transforming growth factor beta receptor II locus was excluded in both families by linkage analysis. A maximum multipoint lod score score of 2.83 was obtained for marker D15S992 (located in the FBN1 gene) in the MF1 family and 1.51 for the same marker in the MF2 family. Two novel mutations of FBN1, p.C271* and p.C637Y, were identified in the MF1 and MF2 families, respectively. CONCLUSIONS: Genotype-phenotype correlations in this study indicate that nonsense mutations of FBN1 may correlate with relatively severe systemic phenotypes when compared with cysteine substitutions, the most common type of FBN1 mutations. Genetic diagnosis for patients with Marfan syndrome would help with genetic counseling, clinical intervention, and prognosis.

[Pay attention to abnormal vision screening for infants and young children].

World Heath Organization (WHO) put forward a global initiative to eliminate avoidable blindness by 2020. The avoidable blindness includes blindness in children such as amblyopia. The critical period of human visual development is from 0 to 3 years old when is just in the period of infancy and young childhood, therefore vision screening for infants and young children should be attached importance, which is critical significant to the children blindness prevention. Due to many aspects of causes, the vision and related risk factor screening for the infants and young children in China is still faced with many challenges. The article strengthened the aspects of the importance of vision screening for infants and young children and put forward some strategies and suggestions.

[The development and importance of molecular diagnosis in hereditary retinal diseases].

Hereditary retinal disease(HRD) is a group of retinal degenerations seen frequently at clinic,which can lead to severe visual impairments or even blindness.Identifying genetic causes and developing advanced and applicable molecular diagnostic tools for HRD is essential to lower the prevalence of HRD, and to find the therapeutic method of HRD. HRD is known to be both clinically and genetically heterogeneous. The large number of causative genes together with the limitation of routine technique hinder the investigators from further investigating the genetic causes of HRD. Targeted genes capture with next-generation high throughput sequencing yield high sensitivity and speed for mutation detection.When compared with traditional techniques, targeted sequencing presents tremendous advantages. Therefore, the development of a powerful molecular diagnostic platform for HRD aims to improve the detection rate of causative genes/mutations in HRD patients, to further investigate the genetic causes for HRD, to better understand the pathological basis of HRD, and to promote the fast development of molecular diagnosis in China. Meanwhile, it will have significance for the clinical and prenatal diagnosis of HRD, and thus providing rationale for gene therapy on HRD.

[Surgical treatment for correcting abnormal complicated head posture in nystagmus].

OBJECTIVE: To demonstrate the surgical choices for patients with complicated head posture associated with nystagmus. METHODS: It was a retrospective clinical study. Thirty-eight cases of congenital nystagmus with abnormal head posture in all three axes without strabismus were retrospectively analyzed. Twenty-nine(76.32%) cases whose dominant head posture were with face turn, 3 cases (7.89%) with chin up or down , respectively, were performed horizontal null zone shift as well as vertical null zone transposition; 2 cases (5.26%) with head tilt as the dominant position were underwent one tendon width transposition of all four vertical muscles;4 cases (10.53%)basically with the same degree for face turn and chip up or down, 2 cases were preferred with recess a group of horizontal yoke muscles and a group of vertical yoke muscles, the other 2 cases were combined with weaken both synergistic oblique muscles. SPSS 13.0 was used to analyse the difference of them. RESULTS: In 29 patients with horizontal head posture dominanted, 15 cases (68.18%) with 25 °-30 ° in horizontal head posture were corrected completely, 5°-15° was the residue for 7 cases (31.82%) with 35 °- 40 °degree in horizontal before surgery. 15 °-20° was residue for 3 cases larger than 40 ° before operation after modified Parks procedure. Anderson procedure can correct the angle of 15°-20° in 4 cases. The horizontal, vertical and torsional components of 22 cases whose predominant head posture were in horizontal with 25°-40° (3.18° ± 1.01°, 4.32° ± 1.14°, 4.55° ± 1.95°) were significantly reduced (t = 63.13, 3.57, 3.95;P < 0.01) after Parks procedure. Recession a group of vertical muscles 5mm or combined with oblique muscles in 3 patients could correct the 20° of vertical head posture, but the improvement of the other two axes was about 5°-10°.One tendon width transposition of all four vertical muscles in 2 cases could correct the 10° of head tilt and 10°-15°of chip up or down. Recession a group of horizontal and vertical muscles can correct 20°-25° of face turn and 20° of vertical head posture. CONCLUSIONS: When head turn with 25°-40°predominates over the vertical and torsional components, recess the horizontal muscles could be effective way in diminishing the abnormal head position on all three axes.When vertical or torsional head posture predominates for the complicated nystagmus, individual designs should be considered.When necessary, reoperations should be needed.

[Targeted sequencing identifies a hotspot mutation SNRNP200 p.S1087L correlates with novel phenotypes in retinitis pigmentosa].

OBJECTIVE: To identify the pathogenic mutation in a four-generation Chinese family with autosomal dominant retinitis pigmentosa (ADRP) and to analyze its associated clinical phenotypes. METHODS: Twelve participants from the index family were recruited, including 5 patients, 6 asymptomatic siblings, and one spouse. All participants underwent ophthalmic examinations, including best-corrected visual acuity (BCVA), visual field (VF) testing, fundus photography, and full-field flash electroretinography (ERG). Targeted sequence capture array technique with next-generation of high throughput sequencing(NGS) was performed to detect variants in 189 hereditary retinal disease (HRD) related genes, comprising 179 identified HRD-causing genes and 10 potential causative genes which were involved in pre-messenger RNA(pre-mRNA) splicing. Variants detected by targeted sequencing were filtered by bioinformatic analyses, validated by Sanger sequencing and intra-familiar analysis.Genotype-phenotype correlation was also analyzed. RESULTS: SNRNP200 p.S1087L was identified as the disease causative mutation for this family by targeted sequencing and optimized bioinformatic analyses. This family demonstrated early onset of the disease by presenting nyctalopia among 6 to 8 years old, performed rapid disease progression and severely impaired visual function by displaying loss of VF among 14 to 17 years old and decreased central vision among 21 to 28 years old. The fundus presentations and ERG results showed typical RP presentations. CONCLUSIONS: SNRNP200 p.S1087L is identified as a hotspot mutation but correlates with distinct phenotypes in the present family, including early onset of the disease, rapid disease progression, and severely impaired visual function. This study also give evidence to that molecular diagnostic platform for HRD can improve the detection rate of causative genes/mutations in HRD patients, thus providing important approaches for further investigation of the genetic causes for HRD.