Publications by authors named "Alvin L Young"

156 Publications

Association of polymorphisms in , and with myopia progression and polygenic risk prediction in children.

Br J Ophthalmol 2021 Apr 2. Epub 2021 Apr 2.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

Aims: To assess the association of single-nucleotide polymorphisms (SNPs) with myopia progression for polygenic risk prediction in children.

Methods: Six SNPs ( rs4373767, rs13382811, rs7744813, rs2073560, rs7839488 and rs524952) were analysed in 1043 school children, who completed 3-year follow-up, using TaqMan genotyping assays. SNP associations with progression in spherical equivalent (SE) were analysed by logistic regression. Polygenic risk scores (PRS) were applied for computing the sum of the risk alleles of multiple SNPs corresponding to myopia progression, weighted by the effect sizes of corresponding SNPs.

Results: rs524952 showed significant association with fast progression (OR=1.32, 95% CI 1.10 to 1.59; p=0.003) and rs7744813 had nominal association (OR=1.32, 95% CI 1.04 to 1.67; p=0.02). In quantitative traits locus analysis, rs524952 and rs7744813 were associated with progression in SE (β=-0.038 D/year, p=0.008 and β=-0.042 D/year, p=0.02) and axial elongation (β=0.016 mm/year, p=0.01 and β=0.017 mm/year, p=0.027). rs13382811 also showed nominal association with faster progression in SE (β=-0.041 D/year, p=0.02). PRS analysis showed that children with the highest PRS defined by rs13382811, rs7744813 and rs524952 had a 2.26-fold of increased risk of fast myopia progression (p=4.61×10). PRS was also significantly associated with SE progression (R=1.6%, p=3.15×10) and axial elongation (R=1.2%, p=2.6×10).

Conclusions: In this study, multi-tiered evidence suggested SNPs in , and as risk factors for myopia progression in children. Additional attention and appropriate interventions should be given for myopic children with high-risk PRS as defined by rs524952, rs7744813 and rs13382811.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318708DOI Listing
April 2021

Transepithelial corneal collagen cross-linking using iontophoresis versus the Dresden protocol in progressive keratoconus: A meta-analysis.

Clin Exp Ophthalmol 2021 Apr 18;49(3):228-241. Epub 2021 Mar 18.

Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Background: Standard epithelium-off collagen cross-linking using Dresden protocol (S-CXL) is the standard of care for progressive keratoconus. Despite its efficacy, epithelial debridement is associated with pain, delayed visual rehabilitation, stromal oedema and haze. Minimising these complications while achieving a comparable efficacy remains an unmet need.

Methods: Comparative studies between transepithelial iontophoresis-assisted CXL (I-CXL) and S-CXL reporting the outcomes of visual, refractive, topographic, aberrometry, demarcation line, endothelial cell density, confocal microscopy or complications were identified from databases. Assessments of publication bias, meta-analyses, sensitivity analysis, subgroup analysis, and meta-regressions were performed.

Results: In this meta-analysis, 586 eyes from three randomised controlled trials and seven comparative studies were analysed. No differences were found in the change in uncorrected/corrected distance visual acuities, mean/maximum keratometry, central corneal thickness, higher order aberration, spherical aberration, coma, subbasal nerve/anterior stromal keratocyte density and demarcation line depth in both CXL protocols (P ≥ .052). However, I-CXL resulted in less thinning at the minimum pachymetry (standardised mean difference 0.25; 95% confidence interval [CI] 0.06-0.44). More importantly, there was a significant reduction in complications following I-CXL (odds ratio 0.30; 95% CI 0.12-0.75). Meta-regression analyses on demarcation line depth and complication suggested that I-CXL was more effective than S-CXL when baseline maximum keratometry was >55.2 D and the risk of complication was independent of other baseline covariates.

Conclusion: I-CXL has a more favourable safety profile, as evidenced by the available literature, with less thinning at the minimum pachymetry and reduced risk of complications while achieving comparable effects on visual, refractive, topographic, aberrometry, and morphological outcomes as S-CXL.
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http://dx.doi.org/10.1111/ceo.13918DOI Listing
April 2021

Independent and Synergistic Effects of High Blood Pressure and Obesity on Retinal Vasculature in Young Children: The Hong Kong Children Eye Study.

J Am Heart Assoc 2021 Feb 26;10(3):e018485. Epub 2021 Jan 26.

Department of Ophthalmology and Visual Sciences The Chinese University of Hong Kong Hong Kong SAR China.

Background High blood pressure (BP) and obesity are becoming increasingly prevalent among children globally. Although prior studies have shown their adverse impacts on macrovascular health, less is known about their effects on microvascular heath. This study aims to evaluate the independent and synergistic effects of hypertensive BP and obesity on retinal vasculature in young children. Method and Results 1006 children aged 6 to 8 years were recruited from the Hong Kong Children Eye Study. Quantitative retinal vascular parameters, including central retinal arteriolar and venular equivalents and retinal arteriolar and venular fractal dimensions, were measured from retinal photographs following a standardized protocol. BP and body mass index were categorized according to reference values from American Academy of Pediatrics and International Obesity Task Force guidelines respectively. Children with hypertensive systolic BP had the narrowest central retinal arteriolar equivalents compared with children with either elevated or normotensive systolic BP (162.4, 164.6, and 167.1 µm; -trend <0.001). Increased standardized systolic BP was associated with narrower central retinal arteriolar equivalents (β=-2.276 µm, <0.001), wider central retinal venular equivalents (1.177, =0.007), and decreased arteriolar fractal dimensions (β=-0.004, =0.034). Children with obesity had the smallest arteriolar fractal dimensions compared with children with overweightness and normal weight (1.211, 1.234, and 1.240; -trend=0.004). Children with both hypertensive BP and either overweightness or obesity had the narrowest central retinal arteriolar equivalents and smallest arteriolar (-trend<0.001 and -trend=0.007). Conclusions Our findings demonstrate the potential synergistic or additive effects for both hypertensive BP and obesity on retinal vasculature in children.
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http://dx.doi.org/10.1161/JAHA.120.018485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955451PMC
February 2021

A Systematic Review on Three Major Types of Scleral-Fixated Intraocular Lens Implantation.

Asia Pac J Ophthalmol (Phila) 2021 Jan 19. Epub 2021 Jan 19.

Department of Ophthalmology & Visual Sciences, Prince of Wales Hospital & Alice Ho Miu Ling Nethersole Hospital, Hong Kong SAR Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR Cornea Service, Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, US.

Purpose: We performed a systematic review on 3 major types of scleral-fixated intraocular lens (SFIOL) implantations and conducted subgroup analyses on pediatric population and subjects with Marfan syndrome.

Design: Systematic review.

Methods: We performed a search in PubMed, Ovid MEDLINE, and Embase for English language articles with keywords "(sutured intraocular lens) OR (SFIOL) OR (sutureless intraocular lens) OR (glued intraocular lens) OR (intrascleral intraocular lens) OR (SFIOL)" through October 16, 2019. Articles reporting individual outcomes after SFIOL were included in this systematic review. Recorded outcome measures included intraoperative and postoperative complications, endothelial cell changes, and intraocular lens-related outcomes.

Results: Our search yielded 217 papers. After removing duplicated and irrelevant reports, we included 57 articles involving 2624 eyes. The mean age at operation was 51.47 ± 25.62 years. Sutured SFIOL was most commonly reported in all subjects with Marfan syndrome and 92.87% of pediatric patients. The pooled intraoperative complication rate was 6.65%. Minor anterior chamber hemorrhage was the most common intraoperative (1.92%) and postoperative complication (13.93%). Optic capture was the top intraocular lens (IOL)-related complication (4.47%). The overall mean endothelial cell loss was 8.95% at 16.77 ± 11.04 months. Overall 11.99% of SFIOLs were decentred with a mean distance of 0.49 ± 0.40 mm and a mean degree of tilt by 4.11 ± 3.03°.

Conclusions: Glued SFIOL had the fewest IOL-related complications and the lowest endothelial cell loss. Sutured SFIOL carried the highest IOL-related complications, whereas sutureless, glueless SFIOL was associated with the greatest endothelial cell loss.
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http://dx.doi.org/10.1097/APO.0000000000000369DOI Listing
January 2021

Management of cytomegalovirus corneal endotheliitis.

Eye Vis (Lond) 2021 Jan 14;8(1). Epub 2021 Jan 14.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Background: Cytomegalovirus (CMV) can manifest as corneal endotheliitis in immunocompetent individuals. Early diagnosis is prudent to prevent endothelial cell loss, which could ultimately lead to corneal decompensation. CMV DNA was first detected in an eye with corneal endotheliitis in 2006; since then, clinical evidence from numerous case reports and case series have accumulated.

Main Text: In this narrative review, we identified several drugs, including ganciclovir, valganciclovir, and their combination in oral, intravenous, intravitreal, and topical forms in different concentrations, together with the judicious use of topical steroids, have reported variable success. There has yet to be any prospective comparative study evaluating the efficacy and safety of these assorted forms of treatment; clinical evidence is based on case reports and case series. CMV endotheliitis presenting with corneal edema can masquerade as other corneal diseases and thus poses a great challenge especially in post-keratoplasty eyes. Heightened awareness is needed before and after keratoplasty to start prompt prophylaxis and treatment.

Conclusion: There is no consensus on the management of CMV endotheliitis. Further studies are much needed to elucidate the optimal treatment modality, regime, and duration in the treatment and prophylaxis of CMV endotheliitis.
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http://dx.doi.org/10.1186/s40662-020-00226-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807491PMC
January 2021

Age Effect on Treatment Responses to 0.05%, 0.025%, and 0.01% Atropine: Low-Concentration Atropine for Myopia Progression Study.

Ophthalmology 2021 Jan 8. Epub 2021 Jan 8.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong SAR, China; Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China; Hong Kong Eye Hospital, Hong Kong SAR, China; Department of Ophthalmology, Hong Kong Children's Hospital, Hong Kong SAR, China. Electronic address:

Purpose: To investigate the effect of age at treatment and other factors on treatment response to atropine in the Low-Concentration Atropine for Myopia Progression (LAMP) Study.

Design: Secondary analysis from a randomized trial.

Participants: Three hundred fifty children aged 4 to 12 years who originally were assigned to receive 0.05%, 0.025%, or 0.01% atropine or placebo once daily, and who completed 2 years of the LAMP Study, were included. In the second year, the placebo group was switched to the 0.05% atropine group.

Methods: Potential predictive factors for change in spherical equivalent (SE) and axial length (AL) over 2 years were evaluated by generalized estimating equations in each treatment group. Evaluated factors included age at treatment, gender, baseline refraction, parental myopia, time outdoors, diopter hours of near work, and treatment compliance. Estimated mean values and 95% confidence intervals (CIs) of change in SE and AL over 2 years also were generated.

Main Outcome Measures: Factors associated with SE change and AL change over 2 years were the primary outcome measures. Associated factors during the first year were secondary outcome measures.

Results: In 0.05%, 0.025%, and 0.01% atropine groups, younger age was the only factor associated with SE progression (coefficient of 0.14, 0.15, and 0.20, respectively) and AL elongation (coefficient of -0.10, -0.11, and -0.12, respectively) over 2 years; the younger the age, the poorer the response. At each year of age from 4 to 12 years across the treatment groups, higher-concentration atropine showed a better treatment response, following a concentration-dependent effect (P <0.05 for each age group). In addition, the mean SE progression in 6-year-old children receiving 0.05% atropine (-0.90 diopter [D]; 95% CI, -0.99 to -0.82) was similar to that of 8-year-old children receiving 0.025% atropine (-0.89 D; 95% CI, -0.94 to -0.83) and 10-year-old children receiving 0.01% atropine (-0.92 D; 95% CI, -0.99 to -0.85). All concentrations were well tolerated in all age groups.

Conclusions: Younger age is associated with poor treatment response to low-concentration atropine at 0.05%, 0.025%, and 0.01%. Among concentrations studied, younger children required the highest 0.05% concentration to achieve similar reduction in myopic progression as older children receiving lower concentrations.
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http://dx.doi.org/10.1016/j.ophtha.2020.12.036DOI Listing
January 2021

Exposure to Secondhand Smoke in Children is Associated with a Thinner Retinal Nerve Fiber Layer: The Hong Kong Children Eye Study.

Am J Ophthalmol 2021 03 29;223:91-99. Epub 2020 Oct 29.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong; Hong Kong Eye Hospital, Hong Kong SAR, China; Department of Ophthalmology, Hong Kong Children's Hospital SAR, China. Electronic address:

Purpose: We sought to assess the effects of exposure to secondhand smoke (SHS) on peripapillary retinal nerve fiber layer (p-RNFL) thickness in children.

Design: Cross-sectional study.

Methods: Children 6-8 years of age were consecutively recruited from the population-based Hong Kong Children Eye Study. All participants received comprehensive ophthalmic examinations and p-RNFL thickness was measured by spectral-domain optical coherence tomography. SHS data were derived from a validated questionnaire. Associations between p-RNFL thickness and SHS exposure status, number of smokers in the family, and quantity of smoking in the family were determined by multivariate linear regression after adjusting for potential confounders.

Results: Among the Hong Kong Children Eye Study cohort (n = 3,103), approximately one-third of children were exposed to SHS (35.4%, n = 1,097). Compared to those without exposure to SHS, children exposed to SHS had similar age (P = .83), gender (P = .17), body mass index (P = .44), birth weight (P = .23), and axial length (P = .34), but had lower family income (P < .001) and lower parental education level (P < .001). After adjusting for all the above factors, exposure to SHS was associated with a thinner global p-RNFL by 4.4 μm (P < .001). Reduced p-RNFL was also associated with increased numbers of smokers in the family (β = -3.40, P < .001) and increased quantity of SHS (β = -0.22, P < .001).

Conclusions: Exposure to SHS in children was associated with a thinner p-RNFL. A thinner p-RNFL may increase the risk of irreversible visual impairment in the future. Our results provide evidence to recommend that children avoid exposure to SHS.
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http://dx.doi.org/10.1016/j.ajo.2020.10.016DOI Listing
March 2021

Genetic associations of myopia severities and endophenotypes in children.

Br J Ophthalmol 2020 Aug 14. Epub 2020 Aug 14.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

Objective: To investigate the associations of multiple single-nucleotide polymorphisms (SNPs) with the severities and endophenotypes of myopia in children.

Methods: A total of 3300 children aged 5-10 years were recruited: 137 moderate and high myopia (SE≤-3.0D), 670 mild myopia (-3.0D-0.5D). 13 SNPs in 13 genes/loci were selected for genotyping in all subjects using TaqMan assays. Associations between each SNP with myopia severities and ocular traits (spherical equivalent (SE), axial length (AL) and corneal radius (CR)) were analysed.

Results: When compared with controls, SNPs rs4373767 (OR=1.15, p=0.038), rs7084402 (OR=1.18, p=0.005) and rs524952 (OR=1.14, p=0.025) showed nominal associations with overall myopia. rs4373767 and rs7084402 showed stronger associations with moderate and high myopia (rs4373767: OR=1.42, p=0.018; rs7084402: OR=1.33, p=0.025), while rs524952 had a stronger association with mild myopia (OR=1.14, p=0.025). rs524952 also showed a difference between emmetropia and hyperopia (p=0.018). In quantitative trait locus analysis, rs4373767, rs7744813 and rs524952 were correlated with both myopic SE (β=-0.09, p=0.03; β=-0.12, p=0.007; β=-0.13, p=0.0006, respectively) and AL (β=0.07, p=0.002; β=0.09, p=0.0008; β=0.07, p=0.0003, respectively). rs7839488 was correlated with both AL (β=0.07, p=0.005) and CR (β=0.02, p=0.006). Moreover, rs4373767-T (β=0.006; p=0.018), rs7744813-A (β=0.007; p=0.015) and rs524952-T (β=0.009; p=0.0006) were correlated with AL-CR ratio.

Conclusions And Relevance: and are genetic risk factors for moderate and high myopia, while and confer risk to excessive AL in children.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316728DOI Listing
August 2020

Association of WNT7B and RSPO1 with Axial Length in School Children.

Invest Ophthalmol Vis Sci 2020 08;61(10):11

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Purpose: To evaluate the association between single-nucleotide polymorphisms (SNPs) in the ZC3H11B, RSPO1, C3orf26, GJD2, ZNRF3, and WNT7B genes and myopia endophenotypes in children.

Methods: Seven SNPs identified in previous genome-wide association studies of axial length (AL) were genotyped in 2883 Southern Han Chinese children. Multiple linear regression analyses were conducted to evaluate the genotype association with AL, spherical equivalent (SE), corneal curvature (CC), and central corneal thickness (CCT).

Results: Two SNPs-namely, rs12144790 in RSPO1 (allele T, P = 0.0066, β = 0.062) and rs10453441 in WNT7B (allele A, P = 8.03 × 10-6, β = 0.103)-were significantly associated with AL. The association of rs4373767 in ZC3H11B (allele C, P = 0.030, β = -0.053) could not withstand the correction for multiple testing. WNT7B rs10453441 showed a strong association with CC (P = 1.17 × 10-14, β = 0.053) and with CCT (P = 0.0026, β = 2.65). None of the tested SNPs was significantly associated with SE. The C allele of SNP rs12321 in ZNRF3 was associated with CC (P = 0.0060, β = -0.018).

Conclusions: This study revealed that the RSPO1 SNP rs12144790 was associated with AL, whereas WNT7B rs10453441 was associated with AL, CC, and CCT in children. A novel association between ZNRF3 rs12321 and CC was discovered. Our data suggest that the RSPO1 and WNT7B genes might exert their effects on multiple aspects of eye growth during childhood. Potential differences in the genetic profiles of AL between children and adults should be explored in larger cohorts.
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http://dx.doi.org/10.1167/iovs.61.10.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441295PMC
August 2020

Outcomes and complications in scleral-fixated intraocular lens implantations.

Int Ophthalmol 2020 Nov 1;40(11):2969-2977. Epub 2020 Jul 1.

Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

Purpose: This study compares outcomes and complications of scleral-fixated intraocular lens implantation between 2 levels of surgeons.

Methods: A retrospective case series of patients undergoing scleral-fixated intraocular lens implantation at Prince of Wales Hospital, Hong Kong, between May 2012 and April 2017 were reviewed. Data collected included age, gender, affected eye, preoperative and postoperative visual acuities, refractive target and outcome, surgeon profile, operative details including method of scleral fixation, intraoperative and postoperative complications and length of follow-up.

Results: Ninety eyes of 90 patients were included for analyses. The mean LogMAR visual acuities were 1.17 ± 0.70 at postoperative week 1, 0.81 ± 0.56 at 1 month, 0.66 ± 0.55 at 3 months, 0.56 ± 0.59 at 6 months, and 0.51 ± 0.60 at 1 year, respectively. After adjusting for age at operation, operative time, axial length, subspecialty of the surgeon and preoperative LogMAR, surgeon seniority was not significantly associated with final visual outcomes. There was no statistically significant difference between the mean improvement in visual acuities between eyes operated by consultants and fellows under direct supervision of a senior surgeon.

Conclusion: Scleral-fixated intraocular lens implantation is safe and effective in improving visual acuity in aphakic adults without capsular support. Under good supervision, fellows were able to produce comparable results compared with experienced specialists.
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http://dx.doi.org/10.1007/s10792-020-01480-8DOI Listing
November 2020

Differential Effects on Ocular Biometrics by 0.05%, 0.025%, and 0.01% Atropine: Low-Concentration Atropine for Myopia Progression Study.

Ophthalmology 2020 12 7;127(12):1603-1611. Epub 2020 Jun 7.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong SAR, China; Hong Kong Eye Hospital, Hong Kong SAR, China. Electronic address:

Purpose: To evaluate changes in ocular biometrics in groups receiving 0.05%, 0.025%, and 0.01% atropine compared with placebo over 1 year based on the Low-Concentration Atropine for Myopia Progression (LAMP) study.

Design: Double-blinded, randomized, placebo-controlled trial.

Participants: Three hundred eighty-three children aged 4 to 12 years who were assigned randomly to receive 0.05%, 0.025%, 0.01% atropine, or placebo once daily in both eyes and completed the first year of the LAMP study.

Methods: Cycloplegic spherical equivalent (SE), axial length (AL), corneal curvature (K), and anterior chamber depth (ACD) were measured by IOLMaster. Corneal astigmatism and lens power were calculated. The ocular biometric parameter changes were compared among groups. Contributions to SE progression from ocular parameters were determined and compared among groups.

Main Outcome Measures: Changes in ocular biometrics and their associations with the changes in SE.

Results: Over 1 year, changes in AL were 0.20 ± 0.25 mm, 0.29 ± 0.20 mm, 0.36 ± 0.29 mm, and 0.41 ± 0.22 mm in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P < 0.001), with a concentration-dependent response. Corneal power remained stable, and its changes were similar across all atropine concentrations: -0.02 ± 0.14 diopter (D), -0.01 ± 0.14 D, -0.01 ± 0.12 D, and 0.01 ± 0.14 D in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P = 0.10). Lens power decreased over time in each concentration, but its changes also were similar across all concentrations: -0.31 ± 0.43 D, -0.38 ± 0.47 D, -0.40 ± 0.43 D, and -0.41 ± 0.43 D in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P = 0.24). Changes in ACD remained similar across all concentrations (P = 0.41). The contributions to SE progression from the ocular biometric changes after adjusting for age and gender in each concentration were similar across all groups (P > 0.05).

Conclusions: Low-concentrations of atropine (0.05%, 0.025%, and 0.01%) have no clinical effect on corneal or lens power. Antimyopic effects of low-concentration atropine act mainly on reducing AL elongation, and therefore could reduce the risk of subsequent myopia complications.
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http://dx.doi.org/10.1016/j.ophtha.2020.06.004DOI Listing
December 2020

Independent Influence of Parental Myopia on Childhood Myopia in a Dose-Related Manner in 2,055 Trios: The Hong Kong Children Eye Study.

Am J Ophthalmol 2020 10 23;218:199-207. Epub 2020 May 23.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong; Hong Kong Eye Hospital, Hong Kong. Electronic address:

Purpose: To determine the effects on childhood myopia of parental myopia, parental education, children's outdoor time, and children's near work.

Design: Population-based cross-sectional study.

Methods: A total of 6,155 subjects in 2,055 family trios (1 child and both parents). Cycloplegic autorefraction was measured for children and noncycloplegic autorefraction for parents. Parental education, children's outdoor time, and near work were collected by questionnaires. Children were categorized into 10 groups based on parental myopia levels. Associations of the above factors with myopia were evaluated by regression analyses. The areas under the receiver operating characteristic curve (AUROCs) for myopia were evaluated.

Results: Mild parental myopia did not increase childhood myopia's risk, but the risk was 11.22-folds when both parents were highly myopic. Higher parental education (Father: OR 1.08, P = .046; Mother: OR 1.11, P = .001) and more reading time of children were risk factors (OR 1.21, P = .044). Reduced odds of myopia were associated with more time spent on outdoor activities (OR 0.78, P = .017). Notably, all these factors became insignificant after adjustment, except for parental myopia. Children with more severe parental myopia spent more time on reading, but less on electronic devices. Parental myopic status alone accounted for 11.82% of myopia variation in children. With age and parental myopia, the AUROC for myopia was 0.731.

Conclusions: Among parental and environmental factors, parental myopia confers, in a dose-related manner, the strongest independent effect on childhood myopia. Therefore children with high risk of myopia can be identified for early prevention, based on parental myopia data.
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http://dx.doi.org/10.1016/j.ajo.2020.05.026DOI Listing
October 2020

Precautionary measures needed for ophthalmologists during pandemic of the coronavirus disease 2019 (COVID-19).

Acta Ophthalmol 2020 05;98(3):221-222

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.

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http://dx.doi.org/10.1111/aos.14438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540674PMC
May 2020

Association of the CAV1-CAV2 locus with normal-tension glaucoma in Chinese and Japanese.

Clin Exp Ophthalmol 2020 07 24;48(5):658-665. Epub 2020 Mar 24.

Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.

Background: The CAV1-CAV2 locus has been associated with primary open-angle glaucoma (POAG) and intraocular pressure. However, its association with normal-tension glaucoma (NTG) was inconclusive. Therefore, we evaluated this association in Chinese and Japanese.

Methods: Two single-nucleotide polymorphisms (SNPs, rs4236601 and rs1052990) from previous genome-wide association studies of POAG were genotyped in a total of 2220 study subjects: a Hong Kong Chinese cohort of 537 NTG patients and 490 controls, a Shantou Chinese cohort of 102 NTG and 731 controls and an Osaka Japanese cohort of 153 NTG and 207 controls. Subgroup analysis by gender was conducted. Outcomes from different cohorts were combined using meta-analysis.

Results: SNP rs4236601 was significantly associated with NTG in the two Chinese cohorts (P = .0019, OR = 4.55, I = 0). In contrast, rs4236601 was monomorphic in the Osaka cohort. The association of rs1052990 was insignificant in a meta-analysis combining Chinese and Japanese cohorts (P = .81, OR = 1.05; I = 64%), and the OR tended towards opposite directions between Chinese (OR = 1.26) and Japanese (OR = 0.69). Gender-specific effects of the SNPs were not statistically significant in the logistic regression or Breslow-day tests of ORs (P > .05), although rs4236601 was significant in males (P = .0068; OR = 10.30) but not in females (P = .14; OR = 2.65) in the meta-analysis of Chinese subjects.

Conclusions: In this study, we confirmed the association of rs4236601 at the CAV1-CAV2 locus with NTG in Chinese. SNP rs4236601 is monomorphic, and rs1052990 tends towards a different direction in the Japanese cohort. Further studies are warranted to verify the ethnic difference and gender-specific effects of this locus.
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http://dx.doi.org/10.1111/ceo.13744DOI Listing
July 2020

Identification of as a susceptibility gene for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

Br J Ophthalmol 2020 Mar 9. Epub 2020 Mar 9.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

Purpose: The endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of the () gene with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using haplotype-tagging single-nucleotide polymorphisms (SNPs) analysis.

Methods: This study involved totally 2343 subjects, including a Hong Kong Chinese cohort (214 nAMD patients, 236 PCV patients and 433 control subjects), a Shantou Chinese cohort (189 nAMD patients, 187 PCV patients and 531 control subjects) and an Osaka Japanese cohort (192 nAMD patients, 204 PCV patients and 157 control subjects). Thirty haplotype-tagging SNPs in were genotyped in the Hong Kong cohort using TaqMan technology. Two SNPs (rs625767 and rs2273717) showing association in the Hong Kong cohort were genotyped in the Shantou and Osaka cohorts. The SNP-disease association of individual and pooled cohorts were analysed.

Results: Two SNPs (rs625767 and rs2273717) showed suggestive association with both nAMD and PCV in the Hong Kong cohort. In the meta-analysis involving all the three cohorts, rs625767 showed significant associations with nAMD (p=0.01; OR=0.82, 95% CI 0.70 to 0.96; I=0%), PCV (p=0.02; OR=0.83, 95% CI 0.71 to 0.97; I=27%) and pooled nAMD and PCV (p=0.002; OR=0.82, 95% CI 0.72 to 0.93; I=0%), with low inter-cohort heterogeneities.

Conclusion: This study revealed as a novel susceptibility gene for nAMD and PCV in Japanese and Chinese. Further studies in other populations are warranted to confirm its role.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315746DOI Listing
March 2020

Two-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study: Phase 2 Report.

Ophthalmology 2020 07 21;127(7):910-919. Epub 2019 Dec 21.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Purpose: To evaluate the efficacy and safety of 0.05%, 0.025%, and 0.01% atropine eye drops over 2 years to determine which is the optimal concentration for longer-term myopia control.

Design: Randomized, double-masked trial extended from the Low-Concentration Atropine for Myopia Progression (LAMP) Study.

Participants: Three hundred eighty-three of 438 children (87%) aged 4 to 12 years with myopia of at least -1.0 diopter (D) originally randomized to receive atropine 0.05%, 0.025%, 0.01%, or placebo once daily in both eyes in the LAMP phase 1 study were continued in this extended trial (phase 2).

Methods: Children in the placebo group (phase 1) were switched to receive 0.05% atropine from the beginning of the second-year follow-up, whereas those in the 0.05%, 0.025%, and 0.01% atropine groups continued with the same regimen. Cycloplegic refraction, axial length (AL), accommodation amplitude, photopic and mesopic pupil diameter, and best-corrected visual acuity were measured at 4-month intervals.

Main Outcome Measures: Changes in spherical equivalent (SE) and AL and their differences between groups.

Results: Over the 2-year period, the mean SE progression was 0.55±0.86 D, 0.85±0.73 D, and 1.12±0.85 D in the 0.05%, 0.025%, and 0.01% atropine groups, respectively (P = 0.015, P < 0.001, and P = 0.02, respectively, for pairwise comparisons), with mean AL changes over 2 years of 0.39±0.35 mm, 0.50±0.33 mm, and 0.59±0.38 mm (P = 0.04, P < 0.001, and P = 0.10, respectively). Compared with the first year, the second-year efficacy of 0.05% and 0.025% atropine remained similar (P >0.1), but improved mildly in the 0.01% atropine group (P = 0.04). For the phase 1 placebo group, the myopia progression was reduced significantly after switching to 0.05% atropine (SE change, 0.18 D in second year vs. 0.82 D in first year [P < 0.001]; AL elongated 0.15 mm in second year vs. 0.43 mm in first year [P < 0.001]). Accommodation loss and change in pupil size in all concentrations remained similar to the first-year results and were well tolerated. Visual acuity and vision-related quality of life remained unaffected.

Conclusions: Over 2 years, the efficacy of 0.05% atropine observed was double that observed with 0.01% atropine, and it remained the optimal concentration among the studied atropine concentrations in slowing myopia progression.
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http://dx.doi.org/10.1016/j.ophtha.2019.12.011DOI Listing
July 2020

High prevalence of myopia in children and their parents in Hong Kong Chinese Population: the Hong Kong Children Eye Study.

Acta Ophthalmol 2020 Jan 24. Epub 2020 Jan 24.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong.

Purpose: To determine the myopia prevalence in Hong Kong Chinese children and their parents.

Methods: It was a population-based cross-sectional study. A total of 4257 children aged 6-8 years, and 5880 parents were recruited in the Hong Kong Children Eye Study. Cycloplegic autorefraction was measured for children; and non-cycloplegic autorefraction for parents. Parental educational level, children's outdoor time, and near work were collected by validated questionnaires.

Results: In children aged 6-8 years, 25.0% were myopic, and among them, 12.7% for the 6-year-olds, 24.4% for the 7-year-olds and 36.1% for the 8-year-old. About 0.7% of children aged 8 years were high myopia. In all age groups, boys (their myopia rate: 13.9% at 6 years, 26.7% at 7 years, and 38.3% at 8 years) were more myopic than girls (11.3% at 6 years, 22.0% at 7 years, 33.4% at 8 years). Among parents, 72.2% were myopic (mother, 73.2%; father, 70.7%) and 13.5% high myopia (mother, 12.8%; father, 14.5%). It was observed that prevalence decreased with ages and increased with education level.

Conclusion: There is a strikingly high prevalence of myopia in Hong Kong children aged 6-8, much higher than that of other regions of China. Of note, the prevalence of children was similar to that in 15 years ago. Furthermore, the myopia prevalence of parents is high, and it had already increased in this cohort. Prevention of childhood myopia is important, likewise for visual complications from high myopia in adults.
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http://dx.doi.org/10.1111/aos.14350DOI Listing
January 2020

Upper Cranial Nerve Involvement and Immunoglobulin G4-Related Optic Neuropathy.

Ophthalmology 2020 05 26;127(5):699-703. Epub 2019 Nov 26.

Department of Ophthalmology and Visual Sciences, Princess of Wales Hospital, Wales, United Kingdom; Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong. Electronic address:

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http://dx.doi.org/10.1016/j.ophtha.2019.11.015DOI Listing
May 2020

Pterygium: Surgical Techniques and Choices.

Asia Pac J Ophthalmol (Phila) 2019 Nov-Dec;8(6):422-423

Department of Ophthalmology & Visual Sciences, Prince of Wales Hospital, Hong Kong SAR.

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http://dx.doi.org/10.1097/APO.0000000000000269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903369PMC
March 2020

Artificial intelligence deep learning algorithm for discriminating ungradable optical coherence tomography three-dimensional volumetric optic disc scans.

Neurophotonics 2019 Oct 1;6(4):041110. Epub 2019 Nov 1.

The Chinese University of Hong Kong, Department of Ophthalmology and Visual Sciences, Hong Kong Special Administrative Region, China.

Spectral-domain optical coherence tomography (SDOCT) is a noncontact and noninvasive imaging technology offering three-dimensional (3-D), objective, and quantitative assessment of optic nerve head (ONH) in human eyes . The image quality of SDOCT scans is crucial for an accurate and reliable interpretation of ONH structure and for further detection of diseases. Traditionally, signal strength (SS) is used as an index to include or exclude SDOCT scans for further analysis. However, it is insufficient to assess other image quality issues such as off-centration, out of registration, missing data, motion artifacts, mirror artifacts, or blurriness, which require specialized knowledge in SDOCT for such assessment. We proposed a deep learning system (DLS) as an automated tool for filtering out ungradable SDOCT volumes. In total, 5599 SDOCT ONH volumes were collected for training (80%) and primary validation (20%). Other 711 and 298 volumes from two independent datasets, respectively, were used for external validation. An SDOCT volume was labeled as ungradable when SS was or when any artifacts influenced the measurement circle or of the peripheral area. Artifacts included (1) off-centration, (2) out of registration, (3) missing signal, (4) motion artifacts, (5) mirror artifacts, and (6) blurriness. An SDOCT volume was labeled as gradable when SS was , and there was an absence of any artifacts or artifacts only influenced peripheral area but not the retinal nerve fiber layer calculation circle. We developed and validated a 3-D DLS based on squeeze-and-excitation ResNeXt blocks and experimented with different training strategies. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were calculated to evaluate the performance. Heatmaps were generated by gradient-weighted class activation map. Our findings show that the presented DLS achieved a good performance in both primary and external validations, which could potentially increase the efficiency and accuracy of SDOCT volumetric scans quality control by filtering out ungradable ones automatically.
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http://dx.doi.org/10.1117/1.NPh.6.4.041110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823275PMC
October 2019

Fifteen-year results of a randomized controlled trial comparing 0.02% mitomycin C, limbal conjunctival autograft, and combined mitomycin C with limbal conjunctival autograft in recurrent pterygium surgery.

Graefes Arch Clin Exp Ophthalmol 2019 Dec 24;257(12):2683-2690. Epub 2019 Oct 24.

Department of Ophthalmology & Visual Sciences, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.

Purpose: To compare the long-term outcomes of recurrent pterygium surgery between three different techniques.

Methods: We performed a 15-year follow-up study of a randomized controlled study on surgical management of recurrent pterygium. Group 1 received limbal conjunctival autograft (LCAU); group 2 received intraoperative mitomycin C (MMC) 0.02% for 5 min; and group 3 received combined LCAU + MMC 0.02% for 5 min. Consecutive patients enrolled in the original study (from April 2001 to March 2003) were invited back for a detailed clinical examination to document the long-term outcomes. The main outcome measures included the recurrence rate, residual conjunctival bed status, and complications from any of the surgical methods.

Results: Sixty-two patients were recruited in the original study. Eight patients had passed away and 12 patients were uncontactable or not responded. One patient who had bilateral operations refused to return for follow-up and one eye had insufficient data for analysis. Finally, 40 eyes of 40 patients were included for analyses. One eye developed a recurrence over 15 years and none required a tertiary pterygium operation. The patient received LCAU for a temporal recurrent pterygium developed a 2.2-mm recurrence.

Conclusions: All three techniques yielded favorable outcomes for patients with recurrent pterygium. The use of LCAU was associated with better cosmetic outcome.
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http://dx.doi.org/10.1007/s00417-019-04499-5DOI Listing
December 2019

Identification and characterization of a novel promoter variant in placental growth factor for neovascular age-related macular degeneration.

Exp Eye Res 2019 10 1;187:107748. Epub 2019 Aug 1.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China. Electronic address:

Purpose: Intronic variants in the placental growth factor (PGF) gene have been associated with neovascular age-related macular degeneration (AMD). This study is to discover and characterize rare variants in the PGF gene for neovascular AMD.

Methods: The promoter region, coding sequences and splicing regions of the PGF gene were sequenced in a Hong Kong southern Chinese cohort of 235 neovascular AMD patients and 435 controls. A detected 18 base-pair deletion variant in the promoter region of PGF was analyzed in a Shantou southern Chinese cohort of 189 neovascular AMD patients and 846 controls. The transcription activity of this disease-associated promoter variant was determined in human ARPE-19 cells by promoter-luciferase analysis.

Results: A novel 18-base-pair deletion mutation in the promoter region of PGF was identified in 3 (1.28%) patients and 1 (0.23%) control subject (OR = 5.61; 95% CI 0.58-54.26) in the Hong Kong cohort, and in 2 (1.06%) patients and 2 (0.24%) controls (OR = 4.51; 95% CI: 0.63-32.25) in the Shantou cohort. In the combined southern Chinese sample, this deletion had a significant association with neovascular AMD (P = 0.026; OR = 5.08, 95% CI: 1.21-21.36). The 18-base-pair deletion was predicted to alter the transcription factor binding sites in the PGF promoter, and higher luciferase expression was detected in ARPE-19 cells transfected with the deletion variant plasmid than those transfected with wild type plasmid (P = 0.0002).

Conclusions: This study identified a rare, functional promoter variant in the PGF gene that increases PGF transcription activity and confers a 5-fold risk to neovascular AMD.
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http://dx.doi.org/10.1016/j.exer.2019.107748DOI Listing
October 2019

Experience of using adalimumab in treating sight-threatening paediatric or adolescent Behcet's disease-related uveitis.

J Ophthalmic Inflamm Infect 2019 Jul 31;9(1):14. Epub 2019 Jul 31.

Department of Ophthalmology & Visual Sciences, Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, Hong Kong SAR.

Purpose: To report the clinical outcomes of adalimumab in treating refractory Behcet's disease (BD)-related uveitis in paediatric or adolescent patients.

Methods: Retrospective review of five paediatric or adolescent patients with BD-related uveitis with a minimum follow-up of 24 months.

Results: Disease quiescence was observed in 9 (90%) of 10 eyes at 12 months. The mean number of relapses per year per patient was 5 (range, 3-7) before initiation of adalimumab treatment. This was reduced to 0.2 relapse per patient per year among the five patients during the first 24 months after starting adalimumab treatment. At baseline, 5 eyes had active retinal vasculitis. Retinal vasculitis resolved in all cases (100%) after starting adalimumab. The mean time to complete resolution of inflammation was 3.4 weeks. The mean ± standard deviation logMAR best-corrected visual acuity was 0.711 ± 0.63 at baseline and improved to 0.172 ± 1.04 at 12 months (P < 0.001). None of the patients developed any adverse events associated with adalimumab treatment.

Conclusion: Adalimumab was effective in preventing irreversible sight-threatening BD-related uveitis in paediatric or adolescent patients. Adalimumab appears to be a promising treatment option for young patients with recalcitrant BD-related uveitis and has a favourable safety profile.
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http://dx.doi.org/10.1186/s12348-019-0181-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669227PMC
July 2019

Detection of glaucomatous optic neuropathy with spectral-domain optical coherence tomography: a retrospective training and validation deep-learning analysis.

Lancet Digit Health 2019 08 9;1(4):e172-e182. Epub 2019 Aug 9.

Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Hong Kong Eye Hospital, Hong Kong Special Administrative Region, China; Prince of Wales Hospital, Hong Kong Special Administrative Region, China.

Background: Spectral-domain optical coherence tomography (SDOCT) can be used to detect glaucomatous optic neuropathy, but human expertise in interpretation of SDOCT is limited. We aimed to develop and validate a three-dimensional (3D) deep-learning system using SDOCT volumes to detect glaucomatous optic neuropathy.

Methods: We retrospectively collected a dataset including 4877 SDOCT volumes of optic disc cube for training (60%), testing (20%), and primary validation (20%) from electronic medical and research records at the Chinese University of Hong Kong Eye Centre (Hong Kong, China) and the Hong Kong Eye Hospital (Hong Kong, China). Residual network was used to build the 3D deep-learning system. Three independent datasets (two from Hong Kong and one from Stanford, CA, USA), including 546, 267, and 1231 SDOCT volumes, respectively, were used for external validation of the deep-learning system. Volumes were labelled as having or not having glaucomatous optic neuropathy according to the criteria of retinal nerve fibre layer thinning on reliable SDOCT images with position-correlated visual field defect. Heatmaps were generated for qualitative assessments.

Findings: 6921 SDOCT volumes from 1 384 200 two-dimensional cross-sectional scans were studied. The 3D deep-learning system had an area under the receiver operation characteristics curve (AUROC) of 0·969 (95% CI 0·960-0·976), sensitivity of 89% (95% CI 83-93), specificity of 96% (92-99), and accuracy of 91% (89-93) in the primary validation, outperforming a two-dimensional deep-learning system that was trained on en face fundus images (AUROC 0·921 [0·905-0·937]; p<0·0001). The 3D deep-learning system performed similarly in the external validation datasets, with AUROCs of 0·893-0·897, sensitivities of 78-90%, specificities of 79-86%, and accuracies of 80-86%. The heatmaps of glaucomatous optic neuropathy showed that the learned features by the 3D deep-learning system used for detection of glaucomatous optic neuropathy were similar to those used by clinicians.

Interpretation: The proposed 3D deep-learning system performed well in detection of glaucomatous optic neuropathy in both primary and external validations. Further prospective studies are needed to estimate the incremental cost-effectiveness of incorporation of an artificial intelligence-based model for glaucoma screening.

Funding: Hong Kong Research Grants Council.
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http://dx.doi.org/10.1016/S2589-7500(19)30085-8DOI Listing
August 2019

Presenting Features, Treatment and Clinical Outcomes of Cytomegalovirus Retinitis: Non-HIV Patients Vs HIV Patients.

Ocul Immunol Inflamm 2020 May 5;28(4):651-658. Epub 2019 Jun 5.

Department of Ophthalmology & Visual Sciences, Chinese University of Hong Kong, Prince of Wales Hospital , Shatin, Hong Kong SAR.

Purpose: To compare clinical features, complications, and outcomes of CMV retinitis in non-HIV immunocompromised patients with HIV infected patients.

Methods: A retrospective study of patients diagnosed with CMV retinitis with or without HIV infection was performed. Results: Thirty-five eyes from 27 patients (median follow up 26 months) were included. Six patients had HIV infection, the others were immunocompromised from a range of causes. The baseline visual acuity (VA) was similar in the two groups. Prevalence of different types of retinitis (fulminant/indolent) was similar in the two groups. Presence of vitreous haze ≥1+ ( = .041), presence of arteritis, ( = .016) and widespread vascular occlusion ( = .003) were more common in the non-HIV group.

Conclusion: CMV retinitis can present with different features depending on the cause of immunocompromise. Evidence of intraocular inflammation such as vitritis, retinal arteritis, and vascular occlusions was more common in HIV-negative subjects.
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http://dx.doi.org/10.1080/09273948.2019.1604003DOI Listing
May 2020

Choroidal thickness in thyroid-associated orbitopathy.

Clin Exp Ophthalmol 2019 Sep 20;47(7):918-924. Epub 2019 May 20.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.

Importance: To investigate the choroidal thickness (CT) in patients with thyroid-associated orbitopathy (TAO).

Background: To compare CT of TAO patients and healthy subjects.

Design: Prospective cross-sectional study in a public hospital.

Participants: One hundred and four eyes of 52 TAO patients and 52 eyes of 26 healthy subjects.

Methods: CT was measured with enhanced-depth imaging optical coherence tomography (EDI-OCT) at the subfoveal, macular and peripapillary regions. Multivariate linear regression was used to evaluate the associations of subfoveal CT with systemic and ocular variables among TAO eyes.

Main Outcome Measures: CT of both groups.

Results: CT of eyes with TAO was significantly increased at the subfoveal region, 1 and 2 mm from the fovea nasally, temporally and superiorly, and 1 mm inferior to the fovea (all P < .05). No significant difference was found in CT at 2 mm inferior to the fovea (P = .094) and all four quadrants of the peripapillary region (superior, P = .096; nasal, P = .732; inferior, P = .179; temporal, P = .052). Among TAO eyes, thinner subfoveal choroid was associated with worsening exophthalmos (P = .043), poorer visual acuity (P = .017), increasing age (P = .040) and axial length (P < .001). There was no association between CT and clinical activity score (P = .239).

Conclusions And Relevance: TAO patients showed thicker choroid than controls over the macula, but not the peripapillary regions. Thinner subfoveal choroid was associated with worsening exophthalmos and poorer vision. EDI-OCT can monitor choroidal vascular changes associated with TAO and its complications.
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http://dx.doi.org/10.1111/ceo.13525DOI Listing
September 2019

Tyrosine kinase inhibitor-induced corneal ulcers.

Lancet Oncol 2019 01;20(1):e65

Department of Ophthalmology & Visual Sciences, Prince of Wales Hospital, Hong Kong; Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(18)30520-5DOI Listing
January 2019

Association of the SIX6 locus with primary open angle glaucoma in southern Chinese and Japanese.

Exp Eye Res 2019 03 23;180:129-136. Epub 2018 Dec 23.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China. Electronic address:

The purpose of the study was to evaluate the association profiles of the SIX6 locus with primary open-angle glaucoma (POAG) in southern Chinese and Japanese. In this study, we tested single marker and haplotype-based associations of 11 tagging single nucleotide polymorphisms (SNPs) covering the SIX6 locus with POAG in a Hong Kong Chinese cohort (N = 1402). A novel SNP (i.e., rs12436579) and two SNPs (i.e., rs33912345 and rs10483727) from previous genome-wide association studies were further tested in a Chinese cohort from Shantou (N = 888) and a Japanese cohort from Osaka (N = 463). Results from the three cohorts were meta-analysed using a random-effect model. We found rs12436579, which has not been previously reported, was associated with POAG in Hong Kong and Shantou Chinese (P = 4.3 × 10, OR = 0.72, I = 0). Additionally, we replicated the association of one known SNP, rs33912345 (P = 0.0061, OR = 0.69, I = 45%), with POAG in the Chinese cohorts but not in the Japanese cohort (P > 0.6). Another known SNP, rs10483727, was nominally associated with POAG in the two Chinese cohorts (P = 0.017, OR = 0.70, I = 53%). All these three SNPs were significantly associated with POAG when the three cohorts were combined in meta-analysis (P<0.005). Furthermore, two haplotypes, C-C (P = 1.13 × 10, OR = 1.41, I = 0) and A-A (P = 0.045, OR = 0.68, I = 70%), defined by rs33912345-rs12436579 were associated with POAG in Chinese but not in Japanese. In conclusion, this study confirmed the association between two GWAS SNPs in SIX6 (rs33912345 and rs10483727) and POAG. Also, a SNP, rs12436579, not associated with POAG before, was found to be associated with POAG in Chinese. Further studies are warranted to elucidate the role of this novel SNP in POAG.
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http://dx.doi.org/10.1016/j.exer.2018.12.014DOI Listing
March 2019

Low-Concentration Atropine for Myopia Progression (LAMP) Study: A Randomized, Double-Blinded, Placebo-Controlled Trial of 0.05%, 0.025%, and 0.01% Atropine Eye Drops in Myopia Control.

Ophthalmology 2019 01 6;126(1):113-124. Epub 2018 Jul 6.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.

Purpose: Low-concentration atropine is an emerging therapy for myopia progression, but its efficacy and optimal concentration remain uncertain. Our study aimed to evaluate the efficacy and safety of low-concentration atropine eye drops at 0.05%, 0.025%, and 0.01% compared with placebo over a 1-year period.

Design: Randomized, placebo-controlled, double-masked trial.

Participants: A total of 438 children aged 4 to 12 years with myopia of at least -1.0 diopter (D) and astigmatism of -2.5 D or less.

Methods: Participants were randomly assigned in a 1:1:1:1 ratio to receive 0.05%, 0.025%, and 0.01% atropine eye drops, or placebo eye drop, respectively, once nightly to both eyes for 1 year. Cycloplegic refraction, axial length (AL), accommodation amplitude, pupil diameter, and best-corrected visual acuity were measured at baseline, 2 weeks, 4 months, 8 months, and 12 months. Visual Function Questionnaire was administered at the 1-year visit.

Main Outcome Measures: Changes in spherical equivalent (SE) and AL were measured, and their differences among groups were compared using generalized estimating equation.

Results: After 1 year, the mean SE change was -0.27±0.61 D, -0.46±0.45 D, -0.59±0.61 D, and -0.81±0.53 D in the 0.05%, 0.025%, and 0.01% atropine groups, and placebo groups, respectively (P < 0.001), with a respective mean increase in AL of 0.20±0.25 mm, 0.29±0.20 mm, 0.36±0.29 mm, and 0.41±0.22 mm (P < 0.001). The accommodation amplitude was reduced by 1.98±2.82 D, 1.61±2.61 D, 0.26±3.04 D, and 0.32±2.91 D, respectively (P < 0.001). The pupil sizes under photopic and mesopic conditions were increased respectively by 1.03±1.02 mm and 0.58±0.63 mm in the 0.05% atropine group, 0.76±0.90 mm and 0.43±0.61 mm in the 0.025% atropine group, 0.49±0.80 mm and 0.23±0.46 mm in the 0.01% atropine group, and 0.13±1.07 mm and 0.02±0.55 mm in the placebo group (P < 0.001). Visual acuity and vision-related quality of life were not affected in each group.

Conclusions: The 0.05%, 0.025%, and 0.01% atropine eye drops reduced myopia progression along a concentration-dependent response. All concentrations were well tolerated without an adverse effect on vision-related quality of life. Of the 3 concentrations used, 0.05% atropine was most effective in controlling SE progression and AL elongation over a period of 1 year.
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http://dx.doi.org/10.1016/j.ophtha.2018.05.029DOI Listing
January 2019

The Evolving Story of Pterygium.

Cornea 2018 Nov;37 Suppl 1:S55-S57

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Pterygium is a fibrovascular subepithelial growth of degenerative tissue over the limbus. It is a common condition worldwide that is especially prevalent in tropical countries within the "pterygium belt." Its exact etiology remains to be elucidated; however, it is strongly associated with exposure to ultraviolet light. The high expression levels of tumor protein p53 (TP53) observed in laboratory studies of pterygium seem to contradict the fast-growing nature of its clinical behavior, and TP53 mutations have been suggested. We demonstrated that mouse double minute 2 (MDM2), a TP53-binding protein, contributes to the inhibition of TP53 activity in human pterygium. Thus, disruption of the MDM2-TP53 interaction should attenuate human pterygium cell growth. For primary pterygium, treatment is relatively straightforward and involves surgical excision. To minimize the risk of recurrence, many adjunctive therapies are adopted, including antimetabolites, such as mitomycin C and 5-fluorouracil, amniotic membrane, different variations on conjunctival and/or limbal conjunctival grafts, and other medications such as anti-vascular endothelial growth factor. In the future, MDM2 antagonists may help further lower the recurrence rates after the treatment of pterygium.
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http://dx.doi.org/10.1097/ICO.0000000000001744DOI Listing
November 2018