Evaluation of NTF4 as a causative gene for primary open-angle glaucoma.

PURPOSE: The neurotrophin-4 (NTF4) gene has been recently implicated in primary open-angle glaucoma (POAG). In this study, we investigated the implication of NTF4 in POAG among three Chinese cohorts. METHODS: The coding regions and exon-intron boundaries of NTF4 was sequenced in 950 unrelated Chinese subjects, including a Hong Kong cohort of 390 patients and 230 controls, a Shantou cohort of 130 patients, and a Beijing cohort of 200 patients. Constructs carrying the detected variants were generated using site-directed mutagenesis and transfected into HeLa cells, followed by solubility and migration analyses. RESULTS: Three variants were identified. p.Pro151Pro was detected in three POAG patients and one control subject. Two novel missense variants, p.Gly157Ala and p.Ala182Val, were identified each in one POAG patient from the Hong Kong cohort, but not in controls. Functional assays showed that the p.Gly157Ala mutant protein was less soluble in Triton X-100, and that migration of HeLa cells transfected with either mutant construct was less than cells transfected with the wildtype. CONCLUSIONS: The NTF4 variants p.Gly157Ala and p.Ala182Val have been shown to be functional mutations, occurring in 2 of a total of 720 Chinese POAG patients. NTF4 is functionally related to POAG pathogenesis but its mutation frequency is low. Therefore, NTF4 does not have a major contribution in the molecular genetics of POAG.

SNP rs1533428 at 2p16.3 as a marker for late-onset primary open-angle glaucoma.

PURPOSE: To investigate the associations between gene variants in cholesterol 24S-hydroxylase (CYP46A1), LIM homeobox transcription factor 1-beta (LMX1B), plexin domain containing 2 (PLXDC2), toll-like receptor 4 (TLR4), transmembrane and tetratricopeptide repeat containing 2 (TMTC2), zona pellucida glycoprotein 4 (ZP4), chromosome 2p16.3, and primary open-angle glaucoma (POAG). METHODS: We studied 462 POAG patients and 577 controls from three cohorts (Hong Kong, Shantou, and Beijing, China). Twelve single-nucleotide polymorphisms (SNPs) were genotyped in the Hong Kong cohort using TaqMan genotyping assay. Significant associations were validated in the Shantou and Beijing cohorts. RESULTS: Association of POAG with TLR4 rs7037117, in a recessive model, was identified in the Hong Kong and Shantou cohorts (both southern Chinese, p(rec)=0.0019) but not the Beijing cohort (northern Chinese). rs1533428 at chromosome 2p16.3 showed a consistent trend of age-specific association in all three cohorts. Genotypes TT + CT conferred a 2.16 fold of significantly increased risk to late-onset POAG (p(dom)=0.00025), but no significant risk to POAG of younger ages of onset in the combined cohort. A joint effect was found between rs7037117 and rs1533428, with carriers of both higher-risk genotypes having a 4.53 fold of increased disease risk (p=0.00028). CONCLUSIONS: Our study reveals discrepant association patterns of 12 candidate SNPs in 7 genes/loci with POAG in Chinese, provides positive replications for POAG markers rs1533428 at 2p16.3 and TLR4 rs7037117, and suggests that rs1533428 is a putative risk variant for late-onset POAG. The identification of an age-specific association between rs1533428 and late-onset POAG highlights a new genotype-phenotype association in POAG. Further studies are warranted to confirm the age-specific association.

Severe and recurrent interface hemorrhage after endothelial keratoplasty.

PURPOSE: To report the occurrence and management of recurrent hemorrhage after Descemet stripping endothelial keratoplasty (DSEK) in a patient with pseudophakic bullous keratopathy. METHODS: An 84-year-old Chinese woman on two oral antiplatelet drugs underwent DSEK in her left eye. Preoperative best-corrected visual acuity was 20/30 OD and 14/200 OS. Intraoperative bleeding was noted from the iris root. Surgery was completed uneventfully, and interface was thoroughly irrigated in the end. Slit lamp examination on the first postoperative day showed a dense interface hemorrhage and an intraocular pressure of 24 mm Hg. Repeat interface irrigation was carried out on postoperative day 4, but the hemorrhage appeared again on the following day. Donor lenticule was well apposed to the corneal stroma, and visual acuity was hand motions in the operated eye. No further surgical interventions were performed. Corticosteroid eye drops were continued four times a day in the operated eye, and the patient was advised weekly follow-up. RESULTS: Over the next 4 weeks, the interface blood gradually started to clear from the central cornea. At the end of 4 months postoperatively, the interface hemorrhage disappeared completely. A final best-corrected visual acuity of 20/80 was achieved. Specular microscopy revealed an endothelial cell density of 1375 cells/mm2. CONCLUSIONS: Interface hemorrhage is a known complication after DSEK surgery. Recurrent hemorrhage may be expected in patients on oral antiplatelet treatment. In cases without associated graft dislocation, conservative management can still result in good visual outcome.

Central serous chorioretinopathy after sequential argon-neodymium: YAG laser iridotomies.

Laser peripheral iridotomy is the standard treatment for acute angle-closure glaucoma. A patient with acute angle-closure glaucoma who developed central serous chorioretinopathy after uneventful laser iridotomies is described. Central serous chorioretinopathy occurring after sequential argon-neodymium:YAG laser peripheral iridotomy is a novel complication in the English literature and is related to the stress induced by both the initial disease and the subsequent procedure, particularly in psychologically susceptible individuals.

Topical atropine in retarding myopic progression and axial length growth in children with moderate to severe myopia: a pilot study.

PURPOSE: To study the safety and efficacy of topical 1% atropine eye ointment in retarding myopic progression in children with moderate to severe myopia. METHODS: This was an interventional control study. Children (aged 5-10 years) with myopia of -3.00 diopters (D) or more were treated with 1% atropine ointment once daily for 1 year. Baseline and regular assessments of refractive errors by cycloplegic autorefraction and of axial length were done by ultrasound biometry, and the results were compared with data of control subjects. RESULTS: Twenty-three children (mean age: 7.4 +/- 1.6 years) with moderate to severe myopia, being treated in the Hong Kong Eye Hospital of the Chinese University of Hong Kong, were recruited into the atropine group, and 23 children from the same eye clinic were matched with the study subjects with respect to age, sex, and initial spherical equivalent refraction, as controls. The initial refractive errors were -5.18 +/- 2.05 D and -5.12 +/- 2.33 D in the atropine and the control groups, respectively (P = 0.934). Myopic progression was significantly less (P = 0.005) in the atropine group (+0.06 +/- 0.79 D) than in the control group (-1.19 +/- 2.48 D). Axial length increase was also significantly smaller in the atropine group (0.09 +/- 0.19 mm) than in the control group (0.70 +/- 0.63 mm) (P = 0.004). One child (4.3%) developed an allergic reaction. No other major adverse effects related to the treatment were noted. CONCLUSION: Topical 1% atropine ointment is a safe and effective treatment for retarding myopic progression in moderate to severe myopia. Further large-scale randomised controlled study with longer follow-up seems warranted.

Clinical characteristics of intermediate uveitis in Chinese patients.

PURPOSE: To describe the clinical characteristics of Chinese patients with intermediate uveitis (IU). METHODS: Retrospective review of patients with IU with at least 6 months follow-up. RESULTS: Seventy patients were identified and the mean follow-up was 59.7 months. The mean age at presentation was 33.1 years. Fifteen (21.4%) patients had disease onset before the age of 18 years; 91.4% of IU cases were considered idiopathic after investigations. At the last follow-up, 85 (74.6%) eyes retained vision of at least 20/40. Poor visual outcome was significantly associated with poor presenting visual acuity (p = .002), presence of epiretinal membrane or atrophic macular changes (p = .003), persistent cystoid macular edema (p = .015), and increased disease duration (odds ratio = 1.015 per month, p = .002). Pediatric patients were more likely to have bilateral (p = .003) and chronic disease (p < .001). CONCLUSIONS: IU in Chinese patients was mainly idiopathic, with good visual outcomes in most patients after appropriate treatment.

Randomized double-masked controlled trial comparing pain scores with and without the use of supplementary 2% lidocaine gel in LASIK.

PURPOSE: To compare pain scores with and without supplementary topical 2% lidocaine gel in patients undergoing simultaneous bilateral laser-assisted in situ keratomileusis (LASIK) under topical anesthesia using 0.5% proparacaine eye drops. DESIGN: Randomized double-masked placebo-controlled trial. METHODS: Fifty-one Chinese subjects (102 eyes, with 51 eyes in each arm) were included. One eye was randomly allocated to have supplementary 2% lidocaine gel while the other eye received carbomer gel as control, in addition to topical 0.5% proparacaine. The pain scores for each eye during microkeratome flap creation, during laser ablation, and at 15, 30, and 45 minutes after LASIK were assessed. An overall pain score of the LASIK procedure was also obtained. Primary outcome measures were pain scores during and after LASIK. Secondary outcomes included need for additional topical anesthesia, patient cooperation score, and duration and complications of surgery. RESULTS: In the 2% lidocaine gel-treated group, the pain scores were significantly lower during microkeratome flap creation and laser ablation, and postoperatively at 30 and 45 minutes (P<.05 for all). Patients in the lidocaine gel group required less additional topical anesthesia (P=.0004) and were more cooperative (P=.019) as compared to the carbomer gel group. No surgical or postoperative complications were observed. CONCLUSIONS: The use of supplementary 2% lidocaine gel in LASIK is effective in lowering the pain experienced during and up to 45 minutes after LASIK.

Differentiation of exudative age-related macular degeneration and polypoidal choroidal vasculopathy in the ARMS2/HTRA1 locus.

PURPOSE: differentiate the associations of exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) with the ARMS2/HTRA1 locus. METHODS: The entire ARMS2 sequence was sequenced and HTRA1 rs11200638 genotyped in 568 unrelated Chinese individuals: 156 exudative AMD patients, 164 PCV patients, and 248 controls. A meta-analysis was performed to examine the effects of rs10490924 and rs11200638 at the ARMS2/HTRA1 locus in PCV. RESULTS: In total, 31 polymorphisms in ARMS2 were identified. Significant associations with both exudative AMD and PCV were observed in 11 of them and HTRA1 rs11200638, with different genotypic distributions between exudative AMD and PCV (P < 0.001). After adjusting for rs11200638, ARMS2 rs10490924 remained significantly associated with exudative AMD (P = 0.011), but not with PCV (P = 0.077). Meta-analysis showed consistent allelic associations of rs10490924 and rs11200638 with PCV in different study populations. CONCLUSIONS: There is a strong and consistent association of the ARMS2/HTRA1 locus with both exudative AMD and PCV, suggesting the two disorders share, at least partially, similar molecular mechanisms. Different effect sizes indicate the existence of additional genetic and environmental factors affecting them to different extents.

Endothelial cell loss and surgically induced astigmatism after sutureless large-incision manual cataract extraction (SLIMCE).

OBJECTIVES: To describe a modified manual cataract extraction technique, sutureless large-incision manual cataract extraction (SLIMCE), and to report its clinical outcomes. METHODS: Case notes of 50 consecutive patients with cataract surgery performed using the SLIMCE technique were retrospectively reviewed. Clinical outcomes 3 months after surgery were analyzed, including postoperative uncorrected visual acuity, best-corrected visual acuity, intraoperative and postoperative complications, endothelial cell loss, and surgically induced astigmatism using the vector analysis method. RESULTS: At the 3-month follow-up, all 50 patients had postoperative best-corrected visual acuity of at least 20/60, and 37 patients (74%) had visual acuity of at least 20/30. Uncorrected visual acuity was at least 20/68 in 28 patients (56%) and was between 20/80 and 20/200 in 22 patients (44%). No significant intraoperative complications were encountered, and sutureless wounds were achieved in all but 2 patients. At the 3-month follow-up, endothelial cell loss was 3.9%, and the mean surgically induced astigmatism was 0.69 diopter. CONCLUSIONS: SLIMCE is a safe and effective manual cataract extraction technique with low rates of surgically induced astigmatism and endothelial cell loss. In view of its low cost, SLIMCE may have a potential role in reducing cataract blindness in developing countries.

Effective antibiotic regime for postoperative acute cholangitis in biliary atresia--an evolving scene.

PURPOSE: The prompt use of empirical antibiotics is vital in managing post-Kasai cholangitis. The authors published findings of their clinical trial in 1991 and established the use of cefoperazone, with a response rate of 88.9%. Here its clinical use since its introduction is reviewed and the trend in its efficacy is assessed. METHODS: A retrospective review was carried out between 1997 and 2003. All episodes of acute cholangitis in patients who underwent Kasai procedure were recorded. Cholangitis was defined as unexplained fever with derangement of liver enzymes. Cefoperazone was started empirically according to the established protocol, and the response to treatment was analyzed. RESULTS: There were 19 patients with a total of 49 episodes of cholangitis. Cefoperazone was used as the first-line empirical antibiotic in 40 of these episodes. Only 30 showed successful response (75%). For the 10 unresponsive episodes, meropenem was used as second-line antibiotic with complete response in all. CONCLUSIONS: The efficacy of cefoperazone in the treatment of post-Kasai cholangitis has decreased over the last years. This suggests a need for a more effective first-line empirical antibiotic. From this review, meropenem seems to be a suitable candidate, and a future prospective clinical trial is warranted.