Tan DO | Ha Noi (original) (raw)

Papers by Tan DO

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Nature genetics, Jul 29, 2017

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a majo... more Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10(-14)) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10(-8)). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the patholo...

$Research paper thumbnail of Comparing combined laser iridoplasty and surgical iridectomy with trabeculectomy in treatment of refractory acute primary angle closure without significant cataract: a randomized controlled trial$

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (... more Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size = -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.

Investigative Ophthalmology & Visual Science, 2015

$Research paper thumbnail of Comparing the Safety and Efficacy of Phacogoniosynechialysis With Phacotrabeculectomy in the Management of Refractory Acute Primary Closure Angle Glaucoma With Cataract: A Multicenter Randomized Trial$

Journal of Glaucoma, 2021

Précis: Combined phacoemulsification-goniosynechialysis (phaco-GSL) and unaugmented phacotrabecul... more Précis: Combined phacoemulsification-goniosynechialysis (phaco-GSL) and unaugmented phacotrabeculectomy were both found to be effective in treating eyes with significant cataract and medically unresponsive acute primary angle closure glaucoma (PACG). Phaco-GSL seemed to be safer, with fewer surgical complications, and achieved better visual acuity than phacotrabeculectomy. Objectives: To compare the results of combined phaco-GSL with unaugmented phacotrabeculectomy in the management of eyes with medically unresponsive acute PACG and cataract. Participants and Research Methods: This was a prospective randomized controlled trial involving patients with significant cataract and acute PACG who were not responsive to maximal medical therapy. Three ophthalmic centers in Hanoi, Vietnam, participated in this trial. Study subjects were randomized into 2 groups: phaco-GSL or phacotrabeculectomy. Of note, mitomycin-C or 5-fluorouracil were not used during trabeculectomy, but postoperative bleb...

JAMA Ophthalmology

The effectiveness of intraocular pressure (IOP) lowering phacoemulsification combined with gonios... more The effectiveness of intraocular pressure (IOP) lowering phacoemulsification combined with goniosynechialysis (GSL) compared with phacoemulsification without GSL remains unknown. OBJECTIVE To compare the IOP outcome after 1 year in patients with synechial primary angle-closure disease (PACD) and cataract who underwent phacoemulsification with intraocular lens implantation (PEI) alone compared with PEI with GSL (PEI-GSL).

Nature genetics, Jan 4, 2016

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a gen... more Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P…

Journal of glaucoma, Jan 21, 2017

To identify the mechanisms of angle closure in the fellow eyes of Vietnamese subjects with unilat... more To identify the mechanisms of angle closure in the fellow eyes of Vietnamese subjects with unilateral primary angle closure glaucoma (PACG) using ultrasound biomicroscopy (UBM) before and after prophylactic laser peripheral iridotomy (LPI). Prospective observational study. Patients diagnosed with PACG in one eye and primary angle closure suspect (PACS) in the other eye were included in this study, conducted from January 2014 to October 2014 at Viet Nam National Institute of Ophthalmology. 112 PACS fellow eyes of 112 patients presenting with unilateral PACG were evaluated. All subjects underwent standard ophthalmic clinical examination and UBM imaging a week before and after LPI. Based on UBM images, the angle closure mechanism was defined according to the classification of Svend Vedel Kessing and John Thygesen as pupillary block(PB),plateau iris(PI) and mixed pattern. The proportion of PACS subjects who showed pupillary block (PB) was 86.6%, while 13.4% showed a plateau iris (PI) co...

Journal of Glaucoma, 2015

Primary congenital glaucoma (PCG, OMIM 231300), the most common glaucoma in infancy, is caused by... more Primary congenital glaucoma (PCG, OMIM 231300), the most common glaucoma in infancy, is caused by developmental defects in the anterior chamber angle. The 3 implicated genes are cytochrome P450 family I subfamily B polypeptide 1 (CYP1B1), latent transforming growth factor β-binding protein 2 (LTBP2), and myocilin (MYOC). In this study, we sought to determine CYP1B1 and MYOC sequence variations in a Vietnamese cohort of index cases with PCG and their families. Thirty Vietnamese subjects with PCG and 120 normal Vietnamese subjects were recruited. PCG was defined by the presence of at least 2 of the following clinical manifestations: increased corneal diameter (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10 mm at birth), corneal edema, Haab&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s striae, optic disc changes, and absence of other ocular or systemic diseases associated with childhood glaucoma. The coding exons, intron and exon boundaries, and untranslated regions of CYP1B1 and MYOC genes were PCR amplified and subjected to bidirectional sequencing in all subjects. We identified 2 homozygous and 3 heterozygous CYP1B1 sequence alterations in our study subjects. Among the 5 mutations identified, 2 (p.H279L and p.L283F) were novel mutations, whereas 3 (p.A121_S122insDRPAFA, p.L107V, and p.V320L) had been previously reported in PCG cases. None of these mutations was observed in any of the 120 controls. Haplotypes generated with 6 non-disease-causing intragenic single nucleotide polymorphisms detected in CYP1B1 indicated that the most common haplotype in Vietnamese population is similar to that found in Chinese and Japanese. The genotype-phenotype correlation showed no significant difference between mutation and no-mutation groups for quantitative clinical features (presenting intraocular pressure, corneal diameter, number of surgeries performed, the cup-to-disc ratio) as well as for qualitative factors (bilateral cases, phenotype severity, and the prognosis) (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). Five out of 30 families with PCG (16.7%) had disease attributable to CYP1B1 alterations suggesting that CYP1B1 is not the major gene causing PCG in Vietnamese unlike in the case of Arab or Romany patients. This percentage is similar to that detected in studies of Japanese and Chinese patients with sporadic PCG. PCG has proven to be an ocular disease of genetic heterogeneity, calling for further studies to identify novel genes causing this disease.

Human molecular genetics, Jan 10, 2015

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease wi... more 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 3,504 POAG cases and 9,746 controls with replication of the most significant findings in 9,173 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=2.81x10(-33)), we observed one SNP showing significant association to POAG (CDC7 - TGFBR3 rs1192415, ORG-allele =1.13, Pmeta=1.60 x 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.

Clinical Ophthalmology, 2014

To compare treatment outcomes with and without silicone oil tamponade in patients undergoing pars... more To compare treatment outcomes with and without silicone oil tamponade in patients undergoing pars plana vitrectomy (PPV) for severe endogenous bacterial endophthalmitis (BEE). One hundred and eight consecutive patients with severe BEE (defined by the absence of pupil red reflex at presentation and/or dense vitreous opacity on ultrasound and no improvement after 24-36 hours of medical treatment) were randomly assigned to two treatment groups: Group 1, standard PPV with intravitreal antibiotics; and Group 2, PPV with intravitreal antibiotics and silicone tamponade. Overall success was defined as: a visual acuity ≥ count fingers at 1 meter, with an attached retina, and no intraocular oil. Fifty three patients were randomized to Group 1 and 55 patients to Group 2. The mean age of study subjects was 32 years and baseline clinical characteristics were similar in both groups. At the final follow-up visit at 9 months, the overall success rate of Group 2 (67.3%) was significantly better than Group 1 (43.4%; P=0.01). There were also fewer devastating complications (such as inoperable retinal detachment, phthisis bulbi) in Group 2 compared with Group 1 (21.8% versus 43.4%; P=0.01). The outcome at 9 months of patients with BEE treated by vitrectomy with silicone oil was better than those treated by vitrectomy alone.

Nature Genetics, 2014

Enteric fever affects more than 25 million people annually and results from systemic infection wi... more Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C(1). We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We observed strong association at rs7765379 (odds ratio (OR) for the minor allele = 0.18, P = 4.5 × 10(-10)), a marker mapping to the HLA class II region, in proximity to HLA-DQB1 and HLA-DRB1. We replicated this association in 595 enteric fever cases and 386 controls from Nepal and also in a second independent collection of 151 cases and 668 controls from Vietnam. Imputation-based fine-mapping across the extended MHC region showed that the classical HLA-DRB1*04:05 allele (OR = 0.14, P = 2.60 × 10(-11)) could entirely explain the association at rs7765379, thus implicating HLA-DRB1 as a major contributor to resistance against enteric fever, presumably through antigen presentation.