Publications by authors named "Fang Yao Tang"

17 Publications

  • Page 1 of 1

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

Non-invasive structural and metabolic retinal markers of disease activity in non-proliferative diabetic retinopathy.

Acta Ophthalmol 2021 Jan 8. Epub 2021 Jan 8.

Department of Ophthalmology, Odense University Hospital, Odense, Denmark.

Purpose: Metabolic and structural microvascular retinal alterations are essential components in diabetic retinopathy (DR). The present study aimed to measure changes at different stages of non-proliferative DR (NPDR) and to explore interactions of imaging-based metrics.

Methods: This cross-sectional, cohort study included 139 eyes from 80 diabetic patients. Each patient underwent dilated fundal examinations including colour fundus photography, retinal oximetry and optical coherence tomography angiography (OCTA), analysed by semi-automated and automated software. Diabetic retinopathy (DR) severity was classified according to the International Clinical Diabetic Retinopathy (ICDR) Severity Scale, ranging from no DR to severe NPDR (level 0-3). Retinal metabolism was evaluated by oximetry as retinal arteriolar (raSatO ) and venular oxygen saturation (rvSatO ), and macular microvascular structure was measured by OCTA as the area of foveal avascular zone (FAZ), vessel density (VD), vessel diameter index (VDI), FAZ circularity and fractal dimension (FD) in the superficial and deep retinal capillary plexus.

Results: A trend for increasing rvSatO was found with increasing DR severity (51.3%, 53.3%, 54.2%, 59.8%, p = 0.02). Increasing severity of DR associated with decreasing FD in the superficial and deep plexus (p < 0.001 and p = 0.014), and in the superficial plexus decreasing VD (p < 0.001), increasing VDI (p = 0.003) and decreasing FAZ circularity (p = 0.006). A few interactions were identified between raSatO , rvSatO and VDI, but only in the deep capillary plexus (p < 0.01 and p < 0.01).

Conclusion: Alterations of the venular retinal vascular oxygen saturation and microvascular structural abnormities were found continuously throughout the DR-spectrum. Given the sparse correlations between metabolic and structural abnormalities, it seems that these occur independently in DR.
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http://dx.doi.org/10.1111/aos.14761DOI Listing
January 2021

Different Effect of Media Opacity on Vessel Density Measured by Different Optical Coherence Tomography Angiography Algorithms.

Transl Vis Sci Technol 2020 07 13;9(8):19. Epub 2020 Jul 13.

Joint Shantou International Eye Center, Shantou University and the Chinese University of Hong Kong, Shantou, China.

Purpose: Several studies show that media opacity reduces vessel density (VD) measured by image processing algorithms of optical coherence tomography angiography (OCTA). However, different models of OCTA designed their own algorithms and computational methods, which may have different effects of opacity on VD. This study is aimed to investigate the impact of a simulated model of media opacity on quantitative measurement of two OCTA devices.

Methods: A spectral-domain based OCTA (Cirrus 5000; Carl Zeiss Meditec) and a swept-source based OCTA (Triton DRI-OCT, Topcon Inc.) were used to image retinal microvasculature at the macula using 3 × 3 mm scanning protocol from 22 eyes of 22 healthy subjects. Media opacity was simulated with neutral-density filters (optical density (OD) ranges 0.10-0.48 in Cirrus; OD ranges 0.15-0.51 in Triton). The filters were placed in front of each study eye, and signal strength (SS) or signal strength intensity (SSI) was recorded during imaging. The parafoveal VD of superficial capillary plexus was then measured using the built-in software from the two devices. The correlations among OD, SS/SSI, and VD were analyzed.

Results: Increased OD was significantly correlated with decreased SS and SSI ( = -0.576 and -0.922, respectively, both < 0.001) in Cirrus and Triton, respectively. Although increased OD was significantly correlated with decreased VD in Cirrus ( = -0.539, < 0.001), there was no significant correlation between OD with VD in Triton ( = -0.143, = 0.137).

Conclusions: The effect of media opacity on quantitative measurement of VD is different between different Cirrus and Triton OCTA devices.

Translational Relevance: This study demonstrates that the effect of media opacity on VD measurement is different among different OCTA devices, suggesting that caution must be taken when interpreting VD measurement on OCTA, particularly among individuals with media opacity.
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http://dx.doi.org/10.1167/tvst.9.8.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422875PMC
July 2020

Different effect of media opacity on automated and manual measurement of foveal avascular zone of optical coherence tomography angiographies.

Br J Ophthalmol 2020 Jul 23. Epub 2020 Jul 23.

Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, China.

Background: Optical coherence tomography angiography (OCTA) provides not only visualisation but also quantitative measurement of foveal avascular zone (FAZ). Media opacity is common in elderly subjects with cataracts. This study aimed to investigate the impact of media opacity on automated and manual FAZ measurement.

Methods: Cirrus 5000 OCTA and Triton OCTA were used to image FAZ using a 3×3 mm scanning protocol from 30 eyes of 30 healthy normal subjects. Media opacity was simulated with neutral-density filters (optical density (OD): 0.10-0.48 in Cirrus 5000 and 0.15-0.51 in Triton). Signal strength (SS) and signal strength intensity (SSI) were provided by the built-in software in Cirrus 5000 and Triton, respectively. FAZ area, perimeter and circularity were measured automatically using the built-in software as well as a customised MATLAB program. FAZ metrics were also measured manually. The correlations between the OD, SS/SSI and FAZ metrics were analysed using Spearman correlation.

Results: Increased OD significantly correlated with decreased SS/SSI ( =-0.602 and -0.925, respectively, both p<0.001), decreased automated FAZ area ( =-0.344 and -0.766, respectively, both p<0.001), but increased manual FAZ area in both Cirrus 5000 and Triton ( =0.423 and 0.543, respectively, both p<0.001). Similar results were found for FAZ perimeter and circularity. There was a positive correlation between SS/SSI with the automated FAZ area but negative correlation with the manual FAZ area.

Conclusions: The effect of media opacity on quantitative measurement of FAZ is different between automated and manual measurements. Cautions must be taken when interpreting FAZ measurement in eyes with media opacity.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315780DOI Listing
July 2020

Clinically relevant factors associated with quantitative optical coherence tomography angiography metrics in deep capillary plexus in patients with diabetes.

Eye Vis (Lond) 2020 3;7. Epub 2020 Feb 3.

1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, Kowloon, China.

Background: To test clinically relevant factors associated with quantitative artifact-free deep capillary plexus (DCP) metrics in patients with diabetes mellitus (DM).

Methods: 563 eligible eyes (221 with no diabetic retinopathy [DR], 135 with mild DR, 130 with moderate DR, and 77 with severe DR) from 334 subjects underwent optical coherence tomography-angiography (OCT-A) with a swept-source OCT (Triton DRI-OCT, Topcon, Inc., Tokyo, Japan). Strict criteria were applied to exclude from analysis those DCP images with artifacts and of poor quality, including projection artifacts, motion artifacts, blurriness, signal loss, B-scan segmentation error, or low-quality score. A customized MATLAB program was then used to quantify DCP morphology from the artifact-free DCP images by calculating three metrics: foveal avascular zone (FAZ), vessel density (VD), and fractal dimension (FD).

Results: 166 (29.5%) eyes were excluded after quality control, leaving in the analysis 397 eyes (170 with no DR, 101 with mild DR, 90 with moderate DR, 36 with severe DR) from 250 subjects. In the multiple regression models, larger FAZ area was associated with more severe DR (β = 0.687;  = 0.037), shorter axial length (AL) (β = - 0.171;  = 0.003), thinner subfoveal choroid thickness (β = - 0.122;  = 0.031), and lower body mass index (BMI) (β = - 0.090;  = 0.047). Lower VD was associated with more severe DR (β = - 0.842;  = 0.001), shorter AL (β = 0.107;  = 0.039), and poorer visual acuity (VA) (β = - 0.133;  = 0.021). Lower FD was associated with more severe DR (β = - 0.891;  < 0.001) and with older age (β = - 0.142;  = 0.004).

Conclusions: Quantitative artifact-free DCP metrics are associated with VA, DR severity, AL, subfoveal choroidal thickness, age, and BMI in diabetic patients. The effects of ocular and systemic factors should be considered for meaningful interpretations of DCP changes in DM patients.
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http://dx.doi.org/10.1186/s40662-019-0173-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996172PMC
February 2020

Repeatability and Agreement of a Swept-Source Optical Coherence Tomography-Based Biometer IOLMaster 700 Versus a Scheimpflug Imaging-Based Biometer AL-Scan in Cataract Patients.

Eye Contact Lens 2020 Jan;46(1):35-45

Department of Ophthalmology and Visual Sciences (T.C.Y.C., K.H.W., F.Y.T., Y.M.W., and C.C.), The Chinese University of Hong Kong, Kowloon, Hong Kong; Hong Kong Eye Hospital (T.C.Y.C.), Kowloon, Hong Kong; and Department of Mathematics and Statistics (M.Y.), Hang Seng Management College, New Territories, Hong Kong.

Purpose: To compare the repeatability and agreement between a swept-source biometer and a Scheimpflug biometer in cataract patients.

Methods: Three consecutive measurements were obtained using a swept-source biometer (IOLMaster 700) and a Scheimpflug biometer (AL-Scan) in 52 eyes of 52 patients. Keratometry, central corneal thickness (CCT), anterior chamber depth (ACD), axial length, and white-to-white (WTW) distance were recorded. Astigmatism values were transformed into vector components of J0 and J45. Intraoperator repeatability was analyzed using intraclass correlation coefficients (ICCs) and reproducibility coefficients (RCs). Agreement of measurements between the two devices was evaluated using the Bland-Altman method.

Results: The IOLMaster 700 showed higher ICCs and lower RCs for the mean keratometry (Km) (P≤0.018), CCT (P≤0.027), and ACD (P≤0.001) measurements, whereas the AL-Scan showed higher ICC and lower RC for the J45 vector component of astigmatism at the 2.4-mm zone (P≤0.034). Both the devices had excellent repeatability (ICC=0.999) in axial length measurement. Systematic differences were found in Km, CCT, ACD, and WTW (P≤0.018) between the devices. The mean difference for Km was -0.196 and -0.144 D measured at the 2.4-mm zone and 3.3-mm zone, respectively. The corresponding mean difference for CCT, ACD, and WTW distance was 14.92 μm, -0.017 mm, and 0.283 mm, respectively. These differences led to a statistically significant but clinically insignificant difference in the prediction of intraocular lens power.

Conclusions: This study showed significant differences in anterior segment measurement repeatability and agreement between a swept-source biometer and a Scheimpflug biometer in eyes with cataract.
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http://dx.doi.org/10.1097/ICL.0000000000000603DOI Listing
January 2020

Quantitative retinal microvasculature in children using swept-source optical coherence tomography: the Hong Kong Children Eye Study.

Br J Ophthalmol 2018 Jun 28. Epub 2018 Jun 28.

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

Aims: To evaluate the distributions of quantitative optical coherence tomography angiography (OCT-A) metrics and its associated factors in children.

Methods: 1059 children aged 6-8 years were recruited from the Hong Kong Children Eye Study. All the participants underwent OCT-A with a swept-source OCT. Retinal microvasculature on superficial capillary plexus was assessed and quantified by a customised automated image analysis programme. Univariable and multiple linear regression analyses were performed to determine systemic (body mass index (BMI), waist circumference, head circumference and blood pressure), demographic and ocular (axial length (AL), macular thickness and volume, retinal nerve fibre layer (RNFL) thickness and visual acuity) variables (independent variables) associated with OCT-A metrics (dependent variables).

Results: In multiple linear regression analyses, enlarged foveal avascular zone area was associated with female gender (β=0.110, p<0.001), decreased AL (β=-0.097, p<0.001) and decreased central macular thickness (β=-0.008, p<0.001). Decreased vessel density was associated with increased BMI (β=-4.12×10, p=0.006), decreased AL (β=0.003, p<0.001) and decreased central macular thickness (β=7.87×10, p=0.001). Increased vessel diameter index was associated with female gender (β=0.020, p=0.007) and decreased AL (β=-0.020, p<0.001). Decreased fractal dimension was associated with older age (β=-0.001, p=0.008). There were no significant correlations between OCT-A metrics with visual acuity, RNFL thickness, central corneal thickness, waist circumference, head circumference and blood pressure (all p>0.05).

Conclusion: Our findings provides new information on baseline morphology of retinal microvasculature and its associated factors in school children, which will be useful for interpreting OCT-A metrics and for identifying and characterising pathological changes in retinal microvasculature.
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http://dx.doi.org/10.1136/bjophthalmol-2018-312413DOI Listing
June 2018

Repeatability, interocular correlation and agreement of quantitative swept-source optical coherence tomography angiography macular metrics in healthy subjects.

Br J Ophthalmol 2019 03 29;103(3):415-420. Epub 2018 May 29.

Joint Shantou International Eye Center, Shantou University & the Chinese University of Hong Kong, Shantou, China

Purpose: To investigate the repeatability, interocular correlation and agreement of quantitative swept-source optical coherence tomography angiography (SS-OCTA) metrics in healthy subjects.

Methods: Thirty-three healthy normal subjects were enrolled. The macula was scanned four times by an SS-OCTA system using the 3 mm×3 mm mode. The superficial capillary map images were analysed using a MATLAB program. A series of parameters were measured: foveal avascular zone (FAZ) area, FAZ perimeter, FAZ circularity, parafoveal vessel density, fractal dimension and vessel diameter index (VDI). The repeatability of four scans was determined by intraclass correlation coefficient (ICC). Then the averaged results were analysed for intereye difference, correlation and agreement using paired t-test, Pearson's correlation coefficient (r), ICC and Bland-Altman plot.

Results: The repeatability assessment of the macular metrics exported high ICC values (ranged from 0.853 to 0.996). There is no statistically significant difference in the OCTA metrics between the two eyes. FAZ area (ICC=0.961, r=0.929) and FAZ perimeter (ICC=0.884, r=0.802) showed excellent binocular correlation. Fractal dimension (ICC=0.732, r=0.578) and VDI (ICC=0.707, r=0.547) showed moderate binocular correlation, while parafoveal vessel density had poor binocular correlation. Bland-Altman plots showed the range of agreement was from -0.0763 to 0.0954 mm for FAZ area and from -0.0491 to 0.1136 for parafoveal vessel density.

Conclusions: The macular metrics obtained using SS-OCTA showed excellent repeatability in healthy subjects. We showed high intereye correlation in FAZ area and perimeter, moderate correlation in fractal dimension and VDI, while vessel density had poor correlation in normal healthy subjects.
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http://dx.doi.org/10.1136/bjophthalmol-2018-311874DOI Listing
March 2019

Author Correction: Determinants of Quantitative Optical Coherence Tomography Angiography Metrics in Patients with Diabetes.

Sci Rep 2018 May 4;8(1):7314. Epub 2018 May 4.

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

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-25619-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935703PMC
May 2018

Genetic Association of the PARL-ABCC5-HTR3D-HTR3C Locus With Primary Angle-Closure Glaucoma in Chinese.

Invest Ophthalmol Vis Sci 2017 08;58(10):4384–4389

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

Purpose: This study evaluates the associations of haplotype-tagging single nucleotide polymorphisms (SNPs) in the PARL-ABCC5-HTR3D-HTR3C region with primary angle closure glaucoma (PACG), with a view to identify the responsible SNP in this region.

Methods: Thirty SNPs from the PARL-ABCC5-HTR3D-HTR3C region were genotyped in a Hong Kong Chinese cohort of 422 PACG patients and 400 control subjects, using TaqMan SNP genotyping assays. Single marker and haplotype-based association analyses were performed.

Results: Two synonymous ABCC5 SNPs, namely rs939336 (p.Cys594=; P = 0.013; odds ratio [OR] = 1.46; 95% confidence interval [CI], 1.08 to 1.97) and rs1132776 (p.Ala395=; P = 0.009; OR = 1.47; 95% CI: 1.10 to 1.95), were associated with PACG. Mild associations were detected for ABCC5 rs9838667 (P = 0.024) and HTR3D rs12493550 (P = 0.035). Conditional analysis revealed that no SNPs remained significant after adjusting for other SNPs, suggesting none of these tagging SNPs is fully responsible for the association in this region. In subgroup analysis, ABCC5 SNPs rs939336, rs1132776, and rs983667 and HTR3D rs12493550 were associated only with the chronic form of PACG. However, these associations could not withstand the correction for multiple testing.

Conclusions: These findings enrich the allelic spectrum of ABCC5 in PACG. We identified no tagging SNP responsible for the association of the whole region. Further deep sequencing analysis of this region should be warranted to uncover whether there is still disease associated variant in this region.
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http://dx.doi.org/10.1167/iovs.17-22304DOI Listing
August 2017

Determinants of Quantitative Optical Coherence Tomography Angiography Metrics in Patients with Diabetes.

Sci Rep 2017 05 31;7(1):2575. Epub 2017 May 31.

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

Early microvascular damage in diabetes (e.g. capillary nonperfusion and ischemia) can now be assessed and quantified with optical coherence tomography-angiography (OCT-A). The morphology of vascular tissue is indeed affected by different factors; however, there is a paucity of data examining whether OCT-A metrics are influenced by ocular, systemic and demographic variables in subjects with diabetes. We conducted an observational cross-sectional study and included 434 eyes from 286 patients with diabetes. Foveal avascular zone (FAZ) area, FAZ circularity, total and parafoveal vessel density (VD), fractal dimension (FD), and vessel diameter index (VDI) from the superficial capillary plexus OCT-angiogram were measured by a customized automated image analysis program. We found that diabetic retinopathy (DR) severity was associated with increased FAZ area, decreased FAZ circularity, lower VD, lower FD, and increased VDI. Enlarged FAZ area was correlated with shorter axial length and thinner central subfield macular thickness. Decreased FAZ circularity was correlated with a reduction in visual function. Decreased VD was correlated with thinner macular ganglion-cell inner plexiform layer. Increased VDI was correlated with higher fasting glucose level. We concluded that the effects of ocular and systemic factors in diabetics should be taken into consideration when assessing microvascular alterations via OCT-A.
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http://dx.doi.org/10.1038/s41598-017-02767-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451475PMC
May 2017

Classification of Exudative Age-Related Macular Degeneration With Pachyvessels on En Face Swept-Source Optical Coherence Tomography.

Invest Ophthalmol Vis Sci 2017 02;58(2):1054-1062

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong 5Department of Ophthalmology, Prince of Wales Hospital, Hong Kong.

Purpose: The purpose of this study was to classify exudative maculopathy by the presence of pachyvessels on en face swept-source optical coherence tomography (SSOCT).

Methods: Consecutive patients with signs of exudative maculopathy underwent SSOCT, fluorescein and indocyanine green angiography (ICGA), ultra-widefield fundus color photography, and autofluorescence examinations. Images were analyzed in a masked fashion by two sets of four examiners in different sessions: (1) the presence of pachyvessels in en face OCT and (2) features of exudative maculopathy in conventional imaging modalities. Quantitative data obtained were subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI), which was the ratio of choroidal vessels lumen area to a specified choroidal area from binarized cross-sectional OCT scans.

Results: Pachyvessels was observed in 38 (52.1%) of 73 eyes. The pachyvessels group was associated with younger age (69.1 ± 9.4 years, odds ratio [OR] = 0.95, 95% confidence interval [95% CI] = 0.90-0.97, P = 0.04), presence of polypoidal lesions (OR = 3.27, 95% CI = 1.24-8.62, P = 0.01), increased SFCT (OR = 1.08, 95% CI = 1.02-1.14, P < 0.01), and increased CVI (65.4 ± 5.3, OR = 1.12, 95% CI = 1.02-1.23, P = 0.01). In multivariate regression, CVI significantly correlated with pachyvessels (OR = 1.24, 95% CI = 1.03-1.55, P = 0.04).

Conclusions: Exudative maculopathy could be classified based on differences in choroidal vasculature morphology. Current results implied that choroidal hemodynamics may be relevant to variable natural history and treatment response in neovascular AMD and polypoidal choroidal vasculopathy.
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http://dx.doi.org/10.1167/iovs.16-20519DOI Listing
February 2017

Choroidal structures in polypoidal choroidal vasculopathy, neovascular age-related maculopathy, and healthy eyes determined by binarization of swept source optical coherence tomographic images.

Graefes Arch Clin Exp Ophthalmol 2017 May 1;255(5):935-943. Epub 2017 Feb 1.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, 4/F Hong Kong Eye Hospital, 147K Argyle Street, Mongkok, Hong Kong, SAR, China.

Purpose: To evaluate quantitatively the choroidal vascularity in polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) patients compared to healthy controls.

Methods: All eyes underwent swept source optical coherence tomography (OCT), and choroidal images were binarized into blood vessels lumen and stroma. The choroidal vascular index (CVI) was defined as the ratio of luminal area (LA) over total choroidal area of the subfoveal region with a width of 1500 μm.

Results: The study included 73 patients with neovascular AMD or PCV with mean ± standard deviation (SD) age of 71.8 ± 9.3 years, which was older than the mean age of 65.1 ± 10.8 years of 72 healthy eyes from control group (p < 0.01). The 44 PCV eyes had significantly higher mean SFCT of 214.23 ± 95.21 μm than neovascular AMD eyes (172.74 ± 96.48 μm, p = 0.03) and greater luminal area (0.23 ± 0.09 mm vs. 0.19 ± 0.08 mm, p = 0.05). After adjusting for age, axial length, and gender in multivariate regression analysis, the SFCT of PCV and neovascular AMD eyes were not significantly different from healthy eyes (195.55 ± 93.11 μm), but the CVI of both PCV (64.94 ± 5.43%, p = 0.01) and neovascular AMD (62.54 ± 5.57%, p = <0.01) were significantly lower than control (68.53 ± 5.91%).

Conclusion: Despite physiological changes of choroidal vasculature due to aging, the choroidal morphology is different in PCV, neovascular AMD and healthy eyes, which has implication on disease pathogenesis.
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http://dx.doi.org/10.1007/s00417-017-3591-3DOI Listing
May 2017

Genetic Associations of Primary Angle-Closure Disease: A Systematic Review and Meta-analysis.

Ophthalmology 2016 06 4;123(6):1211-21. Epub 2016 Feb 4.

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:

Topic: Systematic review and meta-analysis of the genetic associations of primary angle-closure disease (PACD).

Clinical Relevance: To confirm the genetic biomarkers for PACD, including primary angle-closure glaucoma (PACG) and related phenotypes.

Methods: We searched in the MEDLINE and EMBASE databases for genetic studies of PACG or other PACD published from the start dates of the databases to May 11, 2015. We estimated the summary odds ratios (ORs) and 95% confidence intervals (CIs) for each polymorphism in PACG, primary angle-closure suspect (PACS), and primary angle-closure (PAC) using fixed- or random-effect models. We also performed sensitivity analysis to test the robustness of the results.

Results: Our literature search yielded 6463 reports. Among them, we identified 24 studies that fulfilled the eligibility criteria for meta-analysis, involving 28 polymorphisms in 11 genes/loci. We affirmed the association of PACG and combined PACS/PAC/PACG with 10 polymorphisms in 8 genes/loci, including COL11A1 (rs3753841-G, OR, 1.22; P = 0.00046), HGF (rs17427817-C, OR, 2.02; P = 6.9E-07; rs5745718-A, OR, 2.11; P = 9.9E-07), HSP70 (rs1043618, GG+GC, OR, 0.52; P = 0.0010), MFRP (rs2510143-C, OR, 0.66; P = 0.012; rs3814762-G, OR, 1.40; P = 0.0090), MMP9 (rs3918249-C, OR, 1.35; P = 0.034), NOS3 (rs7830-A, OR, 0.80; P = 0.036), PLEKHA7 (rs11024102-G, OR, 1.24; P = 8.3E-05), and PCMTD1-ST18 (rs1015213-A, OR, 1.59; P = 0.00013). Sensitivity analysis indicated that the results were robust.

Conclusions: In this study, we confirmed multiple polymorphisms in 8 genes/loci as genetic biomarkers for PACD, among which 3 were identified in a genome-wide association study (COL11A1, PLEKHA7, and PCMTD1-ST18), and 5 were identified in candidate gene studies (HGF, HSP70, MFRP, MMP9, and NOS3).
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http://dx.doi.org/10.1016/j.ophtha.2015.12.027DOI Listing
June 2016

Association of toll-like receptor 3 polymorphism rs3775291 with age-related macular degeneration: a systematic review and meta-analysis.

Sci Rep 2016 Jan 22;6:19718. Epub 2016 Jan 22.

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

Association of a polymorphism rs3775291 in the toll-like receptor 3 (TLR3) gene with age-related macular degeneration (AMD) had been investigated intensively, with variable results across studies. Here we conducted a meta-analysis to verify the effect of rs3775291 on AMD. We searched for genetic association studies published in PubMed, EMBASE and Web of Science from start dates to March 10, 2015. Totally 235 reports were retrieved and 9 studies were included for meta-analysis, involving 7400 cases and 13579 controls. Summary odds ratios (ORs) with 95% confidence intervals (CIs) for alleles and genotypes were estimated. TLR3 rs3775291 was associated with both geographic atrophy (GA) and neovascular AMD (nAMD), with marginally significant pooled-P values. Stratification analysis by ethnicity indicated that rs3775291 was associated with all forms of AMD, GA and nAMD only in Caucasians (OR = 0.87, 0.78 and 0.77, respectively, for the TT genotype) but not in East Asians. However, the associations could not withstand Bonferroni correction. This meta-analysis has thus revealed suggestive evidence for TLR3 rs3775291 as an associated marker for AMD in Caucasians but not in Asians. This SNP may have only a small effect on AMD susceptibility. Further studies in larger samples are warranted to confirm its role.
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http://dx.doi.org/10.1038/srep19718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726375PMC
January 2016

Circadian Intraocular Pressure Fluctuation and Disease Progression in Primary Angle Closure Glaucoma.

Invest Ophthalmol Vis Sci 2015 Jul;56(8):4994-5005

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China 4Hong Kong Eye Hospital, Kowloon, Hong Kong SAR, China 5Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Shatin, Hong Kong.

Purpose: To document the continuous circadian intraocular pressure (IOP) fluctuation using a contact lens sensor during normal daily activities, and to study the relationship between IOP fluctuation and disease progression in primary angle closure glaucoma (PACG) eyes.

Methods: Circadian IOP fluctuations were recorded by Sensimed Triggerfish sensors in 25 PACG eyes. The sensor output signals were smoothed using B-spline smoothing transform and described by functional data analysis. Glaucoma progression was documented with serial changes in mean deviation (MD) and visual field index (VFI) in Humphrey automated perimetry and retinal nerve fiber layer (RNFL) thickness. The signals were compared between the progressive and stable groups by permutation tests on functional t-statistic.

Results: Statistically significant differences were found from 2200 to 2300 and from 0700 to 0800 in gradients of the IOP fluctuation curve, as well as from 2300 to 2400 and 0800 to 0900 in curvatures of the IOP fluctuation curves, between the progressive MD and stable MD groups (P < 0.05). Significant gradient differences were also found from 1500 to 1600 and 0600 to 0800 between the progressive VFI and stable VFI groups, and from 2400 to 0100 and 0200 to 0300 between the progressive RNFL and stable RNFL groups (P < 0.05).

Conclusions: Significant differences in circadian IOP fluctuation between progressive and stable PACG eyes were identified. Large IOP fluctuations may be associated with disease progression in PACG eyes.
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http://dx.doi.org/10.1167/iovs.15-17245DOI Listing
July 2015

Diabetes mellitus and risk of age-related macular degeneration: a systematic review and meta-analysis.

PLoS One 2014 19;9(9):e108196. Epub 2014 Sep 19.

Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00-1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00-1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44-1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13-1.49) and late AMD (OR, 1.16; 95% CI, 1.11-1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96-1.26), 1.48 (95% CI, 1.44-1.51), and 1.15 (95% CI, 1.11-1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108196PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169602PMC
November 2015