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Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.

Background:The aim was to evaluate changes in choroidal thickness, intraocular pressure (IOP) and other parameters of optical coherence tomography, such as central foveal thickness (CFT), macular volume, peripapillary retinal nerve fibre layer (RNFL) thickness after haemodialysis (HD). Methods: Thirty-four eyes of 34 chronic renal failure patients (9 eyes with diabetic patients) who underwent haemodialysis in the Dialysis Unit of Gangneung Asan Hospital were included. CFT, macular volume, peripapillary RNFL and choroidal thickness were measured before and after haemodialysis by optical coherence tomography (OCT, Spectralis; Heidelberg Engineering). Changes in the IOP were evaluated with Goldmann applanation tonometry before and after haemodialysis. Results: The average choroidal thickness decreased significantly, from 233.1 Ϯ 77.5 mm to 219.1 Ϯ 76.8 mm (paired t-test, p < 0.001). This change correlated with the amount of body weight lost (Pearson's correlation coefficient = 0.348, p = 0.044). The mean IOP decreased from 15.1 Ϯ 2.6 mmHg to 13.9 Ϯ 2.2 mmHg after haemodialysis (paired t-test, p = 0.03). The change in macular volume and the small decrease in CFT (214.0 Ϯ 21.0 mm to 213.8 Ϯ 21.8 mm) were not significant. The measured overall change in RNFL thickness from 93.6 Ϯ 15.5 mm to 94.7 Ϯ 14.6 mm was not significant. Conclusions: Haemodialysis can affect various ocular parameters, particularly choroidal thickness and IOP.

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

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GBE administration slowed the progression of VF damage in patients with NTG, especially in zone 1 corresponding to the superior central field.

PurposeTo investigate whether diurnal fluctuation in intraocular pressure (IOP) can influence the result of the correlations between IOP-related factors and progression of normal tension glaucoma (NTG).MethodsGlaucoma progression was defined as visual field (VF) progression and changes in the optic disc and/or retinal nerve fiber layer (RNFL). Two different methods were used to evaluate the impact of the diurnal fluctuation in IOP. ‘Conventional method’ used in previous studies included all IOP measurements during the follow up time. ‘Time adjusted method’ was used to adjust diurnal fluctuation in IOP with the preferred time. Mean IOP, long term IOP fluctuation and the difference between the lowest and highest IOP were calculated using both methods. Cox regression analyses were performed to evaluate the association between IOP-related factors and NTG progression.ResultsOne hundred and forty eyes of 140 patients with NTG were included in this study. 41% (58 of 140 eyes) of eyes underwent NTG progression. Long term IOP variation calculated by conventional method was not a significant risk factor for NTG progression (hazard ratio[HR], 0.311; 95% confidence interval[CI], 0.056–1.717; P = 0.180). Long term IOP variation calculated by time adjusted method, however, was related to progression, with an HR of 5.260 (95% CI,1.191–23.232; P = 0.029).ConclusionAlthough having the same IOP-related factors, if diurnal fluctuation is included, different results may be found on the relationship between IOP-related factors and NTG progression. Based on our results, diurnal fluctuation in IOP should be considered when IOP-related factors are studied in the future.

Trabeculectomy with mitomycin C-soaked ologen do not seem to exert any synergistic effect with antimetabolites in terms of a reduction in IOP. However, the mitomycin C-soaked collagen matrix implant used in trabeculectomy resulted in comparatively stable IOP and did not aggravate wound healing or scar formation. Encapsulated blebs were generated at a more rapid pace in larger amounts compared with conventional trabeculectomy. The management of encapsulated blebs may be crucial to improving the success rate of surgery.