Fang Yao Tang

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

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.

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

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.

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

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.

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

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.

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

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 mm2 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.

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

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=−4.12×10−4, p=0.006), decreased AL (β=0.003, p<0.001) and decreased central macular thickness (β=7.87×10−5, 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.

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

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.