Harnessing Next-Generation Sequencing as a Timely and Accurate Second-Tier Screening Test for Newborn Screening of Inborn Errors of Metabolism.

In this study, we evaluated the implementation of a second-tier genetic screening test using an amplicon-based next-generation sequencing (NGS) panel in our laboratory during the period of 1 September 2021 to 31 August 2022 for the newborn screening (NBS) of six conditions for inborn errors of metabolism: citrullinemia type II (MIM #605814), systemic primary carnitine deficiency (MIM #212140), glutaric acidemia type I (MIM #231670), beta-ketothiolase deficiency (#203750), holocarboxylase synthetase deficiency (MIM #253270) and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (MIM # 246450). The custom-designed NGS panel can detect sequence variants in the relevant genes and also specifically screen for the presence of the hotspot variant IVS16ins3kb of SLC25A13 by the copy number variant calling algorithm. Genetic second-tier tests were performed for 1.8% of a total of 22,883 NBS samples. The false positive rate for these six conditions after the NGS second-tier test was only 0.017%, and two cases of citrullinemia type II would have been missed as false negatives if only biochemical first-tier testing was performed. The confirmed true positive cases were citrullinemia type II (n = 2) and systemic primary carnitine deficiency (n = 1). The false positives were later confirmed to be carrier of citrullinemia type II (n = 2), carrier of glutaric acidemia type I (n = 1) and carrier of systemic primary carnitine deficiency (n = 1). There were no false negatives reported. The incorporation of a second-tier genetic screening test by NGS greatly enhanced our program's performance with 5-working days turn-around time maintained as before. In addition, early genetic information is available at the time of recall to facilitate better clinical management and genetic counseling.

Dynamic Changes in Long-Standing Multiple Sclerosis Revealed by Longitudinal Structural Network Analysis Using Diffusion Tensor Imaging.

BACKGROUND AND PURPOSE: DTI can be used to derive conventional diffusion measurements, which can measure WM abnormalities in multiple sclerosis. DTI can also be used to construct structural brain networks and derive network measurements. However, few studies have compared their sensitivity in detecting brain alterations, especially in longitudinal studies. Therefore, in this study, we aimed to determine which type of measurement is more sensitive in tracking the dynamic changes over time in MS. MATERIALS AND METHODS: Eighteen patients with MS were recruited at baseline and followed up at 6 and 12 months. All patients underwent MR imaging and clinical evaluation at 3 time points. Diffusion and network measurements were derived, and their brain changes were evaluated. RESULTS: None of the conventional DTI measurements displayed statistically significant changes during the follow-up period; however, the nodal degree, nodal efficiency, and nodal path length of the left middle frontal gyrus and bilateral inferior frontal gyrus, opercular part showed significant longitudinal changes between baseline and at 12 months, respectively. CONCLUSIONS: The nodal degree, nodal efficiency, and nodal path length of the left middle frontal gyrus and bilateral inferior frontal gyrus, opercular part may be used to monitor brain changes over time in MS.

Minimally Invasive Glaucoma Surgery in Primary Angle-Closure Glaucoma.

Primary angle-closure glaucoma (PACG) is responsible for half of the glaucoma-related blindness worldwide. Cataract surgery with or without trabeculectomy has been considered to be the first-line treatment in eyes with medically uncontrolled PACG. While minimally invasive glaucoma surgery has become an important surgical approach for primary open-angle glaucoma, its indications and benefits in PACG are less clear. This review summarizes the efficacy and safety profile of minimally invasive glaucoma surgery in PACG to unfold new insights into the surgical management of PACG.

Latest Developments in Normal-Pressure Glaucoma: Diagnosis, Epidemiology, Genetics, Etiology, Causes and Mechanisms to Management.

Normal-pressure glaucoma (NPG) is part of the spectrum of the open-angle glaucomas and morphologically characterized, as any glaucoma, by a loss of neuroretinal rim parallel to an enlargement and deepening of the optic cup, and development or enlargement of parapapillary beta zone. These morphological characteristics, in addition to the therapeutic benefit of lowering the intraocular pressure (IOP), make NPG differ from vascular-induced optic neuropathy. Based on the anatomy of the optic nerve as a cerebral fascicle, the physiological counter-pressure against the IOP is the orbital cerebrospinal fluid pressure (CSFP), with both pressures forming the trans-lamina cribrosa pressure difference (TLCPD). In contrast to the IOP, the TLCPD is the true pressure exerting force on the optic nerve fibers when passing through the lamina cribrosa. As a theoretical notion, an abnormally high TLCPD due to a low CSFP, in association with a low arterial blood pressure, could therefore be involved in the pathogenesis of NPG. It fits with the finding that the reduction of the IOP (and thus indirectly of the TLCPD) is (the only proven) procedure for NPG therapy. This review additionally highlights the genetic background, diagnostic methods, and therapeutic modalities of NPG.

Degradation of methyl orange and congo red by using chitosan/polyvinyl alcohol/TiO2 electrospun nanofibrous membrane.

In this study, chitosan/polyvinyl alcohol/TiO2 nanofiber was fabricated via electrospinning at a pump rate of 1.5 mL/h and voltage 6 kV. Field-emission scanning electron microscopic images showed bead free finer nanofiber. Fourier transform infrared spectra proved the formation of strong bond among chitosan, polyvinyl alcohol and TiO2. X-ray powder diffraction showed that TiO2 became amorphous in the composite nanofiber. Toughness and thermal stability of the chitosan/PVA nanofibrous membrane was increased with addition TiO2. The chitosan/PVA/TiO2 nanofibrous membrane was stable at basic medium. But degraded in acidic and water medium after 93 and 162 h, respectively. The adsorption mechanism of congo red obeyed the Langmuir isotherm model. On the other hand, adsorption characteristic of methyl orange fitted well with both Langmuir and Freundlich isotherm models. The maximum adsorption capacity of the resulting membrane for congo red and methyl orange is 131 and 314 mg/g, respectively. However, a high dose of adsorbent was required for congo red.

Non-Self-Sealing (Leaky) Anterior Chamber Paracentesis: A New Technique in Managing Postphacoemulsification Intraocular Pressure Rise in Glaucoma and Normal Eyes.

Phacoemulsification (phaco) for cataract extraction is 1 of the most commonly performed ophthalmic surgeries. With increasing evidence of significant intraocular pressure (IOP) reduction after phaco, the paradigm for glaucoma treatment has been shifting toward more cataract extraction instead of glaucoma surgery; thus, the population of glaucoma patients undergoing phaco is likely to continue to increase in the coming years. Although the safety of surgery has improved over the years with newer technologies and machines, postoperative IOP spike remains an important condition even after an uneventful operation. Glaucoma patients undergoing phacoemulsification are particularly at risk of further glaucomatous optic nerve damage from the transient yet potentially high pressures after phaco. Common treatments include topical, intracameral, oral, and systemic IOP-lowering medications; postoperative anterior chamber paracentesis (ACP); and so on. No single treatment to date can guarantee effective prevention or control IOP rise in the first 24 hours after phaco. Sometimes, the IOP remains high despite all of the above treatments and the risk for further glaucomatous damage may be unavoidable. In this perspective article, we discuss the incidence, causes, and treatments of IOP rise after phaco and introduce a new technique, a non-self-sealing (leaky) ACP that may be of use in regulating postoperative IOP rise, especially for patients with glaucoma.

Adsorption study of methyl orange by chitosan/polyvinyl alcohol/zeolite electrospun composite nanofibrous membrane.

The chitosan/polyvinyl Alcohol/zeolite electrospun composite nanofibrous membrane was fabricated for adsorption of methyl orange. The EDX, TGA and tensile test were carried out for the characterization of the membrane. The Young's Modulus of the nanofibrous membranes increased by more than 100% with the addition of zeolite to chitosan/PVA. The batch adsorption tests were conducted by varying the initial concentration of methyl orange, contact time and pH of the dye solution. UV-vis results showed that most of the dye was adsorbed within 6 min. An adsorption kinetic study was carried out using the pseudo-second-order kinetic model, Lagergren-first-order model and intra particle diffusion model. The adsorption kinetics obeyed the Pseudo second order model. The adsorption mechanism was analyzed using the Langmuir and Freundlich isotherm model. The experimental data fits well with the Freundlich model. The adsorption capacity of the membrane was 153 mg/g. Adsorption capacity was decreased with increasing pH value. The resulting nanofiber became less active over methyl orange after several runs.

Effect of deacetylation on property of electrospun chitosan/PVA nanofibrous membrane and removal of methyl orange, Fe(III) and Cr(VI) ions.

In this study, effect of degree of deacetylation on property and adsorption capacity of chitosan/polyvinyl Alcohol electrospun membrane has been investigated. Resulting nanofibers were characterized by FESEM, FTIR, XRD, TGA, tensile testing, weight loss test and adsorption test. FESEM result shows, finer nanofiber was fabricated from 42h hydrolyzed chitosan and PVA blend solution. FTIR and XRD result showed a strong interaction between chitosan and polyvinyl alcohol. Higher tensile strength was observed for the nanofiber having 42h hydrolyzed chitosan. Blend solution of chitosan/PVA having low DD chitosan had higher viscosity. The nanofibrous membrane was stable in distilled water, acidic and basic medium. The isotherm study shows that the adsorption capacity (qm) of nanofiber containing higher DD chitosan was higher for Cr(VI). In contrary, the membrane containing chitosan with lower DD showed the higher adsorption capacity for Fe(III) and methyl orange. Moreover, the effect of DD on removal percentage of adsorbate was dependent on the initial concentration of the adsorbate.

Adsorption of divalent heavy metal ion by mesoporous-high surface area chitosan/poly (ethylene oxide) nanofibrous membrane.

In this study, chitosan/poly (ethylene oxide) nanofibres were fabricated at different chitosan:PEO weight ratio by electrospinning process. The effects of chitosan/PEO composition onto adsorption capability for Cu(II), Zn(II) and Pb(II) ions were studied. Formation of beadless fibres were achieved at 60:40 chitosan:PEO ratio. Average fiber diameter, maximum tensile strength and the specific surface area of the beadless fibres were found to be 115±31nm, 1.58MPa and 218m2/g, respectively. Chitosan/PEO composition that produced beadless fibres tend to possess higher hydrophilicity and maximum specific surface area. These characteristics lead the beadless fibres to the maximum adsorption capability. Adsorption equilibrium data were analysed by Langmuir and Freundlich isotherm. Freundlich isotherm showed the better fit with the experimental data and proved the existence of the monolayer adsorption conditions. The maximum adsorption capacity of the beadless fibres for Cu(II), Zn(II) and Pb(II) ions were found to be 120, 117 and 108mgg-1, respectively.

Preliminary results of CO2 laser-assisted sclerectomy surgery (CLASS) in the treatment of advanced glaucoma in a Chinese population.

To evaluate the efficacy and safety of CO2 laser-assisted sclerectomy surgery (CLASS) in Chinese patients with advanced glaucoma.Patients with advanced glaucoma who were candidates for glaucoma filtration surgery were included. The intraocular pressure (IOP) and number of antiglaucoma medications were documented before surgery and at all postoperative clinic visits. All intra- and postoperative complications were documented. The primary outcome measures were the changes in IOP and medication use before and after the procedure as well as complications from the procedure. The secondary outcome measure included the CLASS success rate.Twenty patients (23 eyes) underwent CLASS between November 2014 and September 2015. Nineteen eyes had primary open-angle glaucoma, 2 eyes had primary angle-closure glaucoma, and 2 eyes had uveitic glaucoma. One patient was lost to follow-up. The mean age of subjects was 68.1 ±â€Š11.9 years. IOP was significantly reduced at 1 day and 1 week after CLASS. At 6 months, the IOP and number of medications were significantly reduced by 19.0% and 38.2%, respectively (both P < 0.0001). One patient had intraoperative trabeculo-Descemet membrane perforation. Two patients required laser goniopuncture and 2 required needling between 3 and 6 months postoperatively. The overall success rate was 81.8% at 6 months.CLASS achieved a modest IOP reduction in the early postoperative period and was overall a safe procedure for advanced glaucoma.

Incidence and Risk Factors of Retinopathy of Prematurity From 2 Neonatal Intensive Care Units in a Hong Kong Chinese Population.

PURPOSE: To determine the incidence and risk factors of retinopathy of prematurity (ROP) in very low birth weight (VLBW) preterm Chinese infants. DESIGN: Retrospective review. METHODS: Medical records were reviewed for all neonates screened for ROP between January 2007 and December 2012 in Hong Kong. Screening was offered to VLBW (≤1500 g) and/or preterm (gestation, ≤32 weeks) neonates using the Royal College of Ophthalmologists ROP guideline and the International Classification of ROP by 3 pediatric ophthalmologists. Maternal and neonatal covariates were analyzed using univariate and multivariable logistic regression analyses for both ROP and type 1 ROP. RESULTS: Of the 513 screened infants, the mean gestational age (GA) was 30.0 ± 2.5 weeks and the mean birth weight (BW) was 1232.6 ± 325.2 g. The incidence of ROP and type 1 ROP was 18.5% and 3.7%, respectively. In univariate analysis, a lighter BW, lower GA, blood transfusion, patent ductus arteriosus, nonsteroidal anti-inflammatory drug use, postnatal hypotension, inotropes usage, low Apgar scores, sepsis, mechanical ventilation, supplementary oxygen use, respiratory distress syndrome, anemia, surfactant use, and bronchopulmonary dysplasia were found to be associated with the development of both ROP and type 1 ROP (P < 0.05). In multivariable logistic regression analysis, BW, GA, and intraventricular hemorrhage were significant risk factors for ROP. Preeclampsia and eclampsia were the only protective factors for ROP development on multivariable logistic regression analysis (P = 0.02). CONCLUSIONS: In VLBW preterm Chinese infants, lower GA, lighter BW, and intraventricular hemorrhage were significant risk factors for ROP, whereas preeclampsia and eclampsia were protective.

Accuracy of Intraocular Lens Power Calculation Formulas for Highly Myopic Eyes.

Purpose. To evaluate and compare the accuracy of different intraocular lens (IOL) power calculation formulas for eyes with an axial length (AL) greater than 26.00 mm. Methods. This study reviewed 407 eyes of 219 patients with AL longer than 26.0 mm. The refractive prediction errors of IOL power calculation formulas (SRK/T, Haigis, Holladay, Hoffer Q, and Barrett Universal II) using User Group for Laser Interference Biometry (ULIB) constants were evaluated and compared. Results. One hundred seventy-one eyes were enrolled. The Barrett Universal II formula had the lowest mean absolute error (MAE) and SRK/T and Haigis had similar MAE, and the statistical highest MAE were seen with the Holladay and Hoffer Q formulas. The interquartile range of the Barrett Universal II formula was also the lowest among all the formulas. The Barrett Universal II formulas yielded the highest percentage of eyes within ±1.0 D and ±0.5 D of the target refraction in this study (97.24% and 79.56%, resp.). Conclusions. Barrett Universal II formula produced the lowest predictive error and the least variable predictive error compared with the SRK/T, Haigis, Holladay, and Hoffer Q formulas. For high myopic eyes, the Barrett Universal II formula may be a more suitable choice.

Efficacy and Safety of Trabectome Surgery in Chinese Open-Angle Glaucoma.

To investigate the clinical outcome of the Trabectome in Chinese open-angle glaucoma (OAG). This prospective case series recruited pseudophakic glaucoma subjects with open-angle configuration. Trabeculectomy ab interno was performed using the Trabectome to 120° of the trabecular meshwork. Intraocular pressure (IOP) and medications were recorded preoperatively and every 3 months postoperatively. Visual acuity was measured preoperatively and at 1 and 6 months postoperatively. One-way ANOVA with Tukey Multiple Comparison Test were used to measure the pre and postoperative parameters. In 19 eyes of 19 Chinese subjects, 26.3% were uveitic, 68.4% were primary open-angle glaucoma, and 5.3% had a history of chronic angle-closure glaucoma with open-angles after cataract extraction. The subjects' mean age was 67.5 ±â€Š14.4 years, with 4 females and 15 males. Two patients required secondary filtration procedure. At 6 months, the IOP reduced by 34.8% (24.4 ±â€Š4.4 mm Hg to 15.9 ±â€Š5.1 mm Hg, P < 0.0001). The number of types of antiglaucoma medications was reduced by 28.2% (3.9 ±â€Š0.8-2.8 ±â€Š1.6, P < 0.0001). The visual acuity was static at 1 and 6 months postoperatively (P = 0.4). There were no intraoperative complications. 26.3% of subjects had a transient IOP spike > 21 mm Hg, 1 had hyphema requiring washout, and 1 had reactivation of herpetic keratitis. The success rate at 6 months was 89.5%. Trabectome achieved a modest reduction in IOP and medications in the majority of pseudophakic Chinese OAG eyes.

A review of selective laser trabeculoplasty in the Hong Kong Chinese population.

INTRODUCTION: Selective laser trabeculoplasty was first introduced to Hong Kong in 2004 for intra-ocular pressure lowering in the treatment of primary glaucoma. Since then, it has gained popularity as an alternative to anti-glaucoma medications and as a bridging therapy prior to more invasive glaucoma surgeries because of the high safety profile of the laser. METHODS: An Ovid search was performed using "selective laser trabeculoplasty" as the key word, which identified 190 unique articles; 24 reviews and/or meta-analyses were excluded. All remaining abstracts of original articles were in English. This review particularly focuses on the local population by summarising the findings from peer-reviewed publications that involved a Hong Kong Chinese population. RESULTS AND CONCLUSION: This review addresses some of the clinically relevant questions relating to selective laser trabeculoplasty including laser application, optimal energy, efficacies and success rates among different glaucoma subtypes, predictors of success, adverse effects, and intra-ocular pressure fluctuation after selective laser trabeculoplasty.

Assessment of corneal biomechanical parameters in myopes and emmetropes using the Corvis ST.

BACKGROUND: Prior studies have demonstrated conflicting results regarding the relationship between corneal biomechanical properties and refractive error. Thus, the purpose of this study was to compare the corneal biomechanical parameters of myopes and emmetropes. METHODS: Ninety-four subjects with varying degrees of myopia (aged 29 to 74 years, spherical equivalent [SE] -0.5 to -17.5 D) and 25 emmetropes (aged 19 to 75 years, SE: -0.5 to +0.5 D) presenting at the Queen Mary Hospital, Hong Kong were recruited sequentially for this prospective study. All patients were phakic with no history of coexisting ocular disease. The corneal biomechanical parameters of the right eye of each subject were analysed using the Corvis ST non-contact tonometer. Intraocular pressure (IOP) was measured using both the Corvis ST and the Topcon Non-Contact Tonometer CT-80. Refractive error was measured by non-cycloplegic subjective and objective refractometry. RESULTS: High myopes (SE greater than -6.00 D) demonstrated greater mean outward applanation velocities (p < 0.001) and peak distance measurements (p = 0.009) compared to both low to moderate myopes (SE -0.50 to -6.00 D) and emmetropes. Both outward applanation velocity and peak distance were moderately correlated with refractive error (p ≤ 0.001), strongly correlated with IOP and weakly correlated with central corneal thickness. There were no statistically significant differences in age, IOP or central corneal thickness among emmetropes, low to moderate myopes or high myopes. CONCLUSION: Within this study of Chinese subjects, high myopes demonstrate greater corneal mean outward applanation velocity on Corvis ST testing, than emmetropes. In particular, those with high myopia (SE greater than -6.00 D) show a distinct corneal biomechanical profile relative to those with either emmetropia or low to moderate myopia using the Corvis ST.

Developments in laser trabeculoplasty.

Laser trabeculoplasty has an increasing important role in the management of glaucoma as more emphasis is placed on minimally invasive therapies. In recent years, the following laser trabeculoplasty technologies have been introduced: micropulse laser trabeculoplasty, titanium-sapphire laser trabeculoplasty and pattern scanning trabeculoplasty. These lasers help to reduce the intraocular pressure (IOP) and the burden of glaucoma medical therapy. Literature findings regarding the safety and efficacy of these newer forms of laser trabeculoplasty in the treatment of open-angle glaucoma is summarised. These relatively newer procedures appear to have similar efficacy when compared with the former selective laser trabeculoplasty or argon laser trabeculoplasty. In addition, they potentially offer a more favourable safety profile with fewer complications, including postlaser inflammation and IOP spikes. Further large-scale studies are necessary to evaluate the long-term benefits of these newer forms of laser trabeculoplasty. Their initial promising results offer patients with glaucoma additional treatment alternatives.