Improved accuracy of spectral-domain optical coherence tomography and optical coherence tomography angiography for monitoring myopic macular neovascularisation activity.

BACKGROUND/AIMS: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD OCT) combined with OCT angiography (OCTA) for myopic myopic macular neovascularisation (MNV) activity. METHODS: Both eyes of patients with myopic MNV diagnosed with fluorescein angiography (FA), SD OCT and OCTA were assessed by unmasked investigators. The images were deidentified and randomised before graded by masked investigators, who determined the presence of active myopic MNV by using SD OCT together with OCTA without FA and by FA alone, respectively. The findings of masked investigators were compared with unmasked investigators. RESULTS: 213 eyes of 110 patients comprising 499 imaging episodes were eligible for grading. For diagnosing new-onset myopic MNV without FA, combined use of SD OCT and OCTA had a sensitivity of 0.94, specificity of 0.84 and area under the curve (AUC) of 0.92. FA had a sensitivity of 0.52 (p<0.01), specificity of 0.80 (p=0.38) and AUC of 0.66 (p<0.01). For recurrent myopic MNV, the combination of SD OCT and OCTA had a sensitivity of 0.98, specificity of 0.78 and AUC of 0.88. FA had a sensitivity of 0.50 (p=0.04), specificity of 0.76 (p=0.85) and AUC of 0.63 (p=0.01). Myopic traction maculopathy was more frequently associated with recurrent myopic MNV (p<0.01). CONCLUSION: SD OCT with dense volumetric scan was highly sensitive for diagnosing myopic MNV. The addition of OCTA improved the diagnostic specificity without FA. Monitoring of the longitudinal changes on SD OCT and judicious use of FA is a reliable surveillance strategy for myopic MNV.

Advances in myopia control strategies for children.

Myopia has long been a global threat to public health. Timely interventions are likely to reduce the risk of vision-threatening complications. There are both established and rapidly evolving therapeutic approaches to slow myopia progression and/or delay its onset. The effective methods for slowing myopia progression include atropine eye-drops, defocus incorporated multiple segments (DIMS) spectacle lenses, spectacle lenses with highly aspherical lenslets target (HALT), diffusion optics technology (DOT) spectacle lenses, red light therapy (RLT), multifocal soft contact lenses and orthokeratology. Among these, 0.05% atropine, HALT lenses, RLT and +3.00 peripheral addition soft contact lenses yield over 60% reduction in myopia progression, whereas DIMS, DOT and MiSight contact lenses demonstrate at least 50% myopia control efficacy. 0.05% atropine demonstrates a more optimal balance of efficacy and safety than 0.01%. The efficacy of 0.01% atropine has not been consistent and requires further validation across diverse ethnicities. Combining atropine 0.01% with orthokeratology or DIMS spectacles yields better outcomes than using these interventions as monotherapies. Increased outdoor time is an effective public health strategy for myopia prevention while recent studies suggest that 0.05% low-concentration atropine and RLT therapy have promising potential as clinical myopia prevention interventions for high-risk groups. Myopia control spectacle lenses, being the least invasive, are safe for long-term use. However, when considering other approaches, it is essential to ensure proper instruction and regular follow-ups to maintain safety and monitor any potential complications. Ultimately, significant advances have been made in myopia control strategies, many of which have shown meaningful clinical outcomes. However, regular use and adequate safety monitoring over extended durations are imperative to foster confidence that can only come from extensive clinical experience.

Influence of secondhand smoke exposure on the retinal vasculature of children in Hong Kong.

BACKGROUND: A recent prospective demonstrated that cardiovascular risk factors in early childhood were associated with later cardiovascular events. However, the impact of secondhand smoke (SHS) on children is unclear. The aims of this study is to determine the effects of SHS exposure on the retinal vasculature of children. METHODS: This is a population-based cross-sectional study of children aged 6 to 8 years. All participants received comprehensive ophthalmic examinations and retinal photography. Data on SHS exposure was derived from a validated questionnaire. A validated deep-learning system was used to automatically estimate retinal arteriolar and venular calibers from retinal photographs. Associations of quantitative retinal vessel caliber values with SHS exposure, number of smokers in the household, and total number of cigarettes smoked were determined by analyses of covariance (ANCOVA) after adjusting for potential confounders. Test of trend was determined by treating categorical risk factors as continuous ordinal variables. RESULTS: Here we show children exposed to SHS have wider retinal arteriolar (CRAE 152.1 µm vs. 151.3 µm, p < 0.001) and venular (CRVE 216.7 µm vs. 215.5 µm, p < 0.001) calibers compared to those in smoke-free homes, after adjustment for different factors. Wider arteriolar and venular calibers are also associated with increasing number of smokers in the family (p trend < 0.001) and more cigarettes smoked among family smokers (p trend<0.001). CONCLUSIONS: Exposure to SHS at home is associated with changes in retinal vasculature among children. This reinforces the adverse effect of secondhand smoking around children though further research incorporating comprehensive assessment of potential confounders is necessary.

Exposure to secondhand smoke can be harmful, particularly for our heart and lung health as adults. However, the impact of secondhand smoke on children is less clear. Here, we looked at the effects of secondhand smoke exposure on vessels within children's eyes. The health of these vessels is a potential indicator of overall eye health and is also associated with cardiovascular disease. Pictures were taken of children's eyes and analyzed using a computer program. We looked at the association between vessel measurements in the eye and how much secondhand smoke the children are exposed to. We observed differences in the vessels in children exposed to secondhand smoke, compared to those from smoke-free homes. These findings indicate that secondhand smoke may affect the health of children's eyes and highlight the need to promote smoke-free home environments.

Pathogenesis of myopic choroidal neovascularization: A systematic review and meta-analysis.

Myopic choroidal neovascularization (CNV) is a vision-threatening complication of high myopia. Here, we systematically review cohort, case-control, and cross-sectional studies in PubMed, Embase, and Web of Science, and summarize the associated factors of myopic CNV using meta-analysis where applicable. Among 1,333 records assessed, 50 were found eligible, all having a low-to-moderate risk of bias. Highly myopic eyes with CNV had a higher risk of lacquer cracks (odds ratio = 2.88) and patchy chorioretinal atrophy (odds ratio = 3.43) than those without. The mean posterior staphyloma height (µm) was greater in myopic CNV eyes than in highly myopic eyes without CNV (mean difference = 82.03). The thinning of choroidal thickness (µm) between myopic eyes with and without CNV differed significantly (mean difference = -47.76). The level of vascular endothelial growth factor (pg/ml) in the aqueous humor of myopic CNV eyes was significantly higher than in highly myopic eyes without CNV (mean difference = 24.98), the same as interleukin-8 (IL-8) (pg/ml, mean difference = 7.73). Single-nucleotide polymorphisms in the vascular endothelial growth factor, complement factor I, and collagen type VIII alpha 1 genes were associated with myopic CNV. We found that myopic CNV eyes have a higher ratio of lacquer cracks and patchy chorioretinal atrophy, thinner choroid, greater posterior staphyloma height, and a higher level of vascular endothelial growth factor and IL-8 in aqueous. Structural predisposing lesions, hemodynamic, genetic, and systemic factors are also associated with myopic CNV.

Association of Polymorphisms in ZFHX1B and PAX6 With Anisometropia in Chinese Children: The Hong Kong Children Eye Genetics Study.

Purpose: To identify gene variants associated with anisometropia development in children. Methods: This is a population-based, cross-sectional, and longitudinal genetic association study involving 1057 children aged 6 to 10 years with both baseline and 3-year follow-up data. Six single nucleotide polymorphisms (SNPs), ZC3H11B rs4373767, ZFHX1B rs13382811, KCNQ5 rs7744813, SNTB1 rs7839488, PAX6 rs644242, and GJD2 rs524952 were analyzed in all children. Anisometropia was defined by an interocular difference in SE of ≥1 diopter (D) (Aniso-SE) and an interocular difference in axial length (AL) of ≥0.3 mm (Aniso-AL), respectively. Genetic associations of individual SNPs and joint SNP effects were analyzed. Results: ZFHX1B rs13382811 was associated nominally with Aniso-AL (odds ratio [OR], 1.66; P = 0.003) at baseline. At 3 years, rs13382811 was significantly associated with Aniso-AL (OR, 1.49; P = 0.001) and became nominally associated with Aniso-SE (OR, 1.40; P = 0.01). In addition, PAX6 rs644242 was significantly associated with Aniso-AL at 3 years (OR, 1.45; P = 0.002). At the 3-year follow-up, PAX6 rs644242 was associated significantly with Aniso-AL development (OR, 1.61; P = 0.0003) and nominally with Aniso-SE development (P = 0.03) in children who were not anisometropic at baseline, whereas ZFHX1B rs13382811 was associated nominally with Aniso-AL development (P = 0.02). An additive SNP analysis indicated children carrying the risk allele T of ZFHX1B rs13382811 and allele A of PAX6 rs644242 might have a 4.33- and 6.90-fold of increased risk of Aniso-SE and Aniso-AL development by 3 years, respectively. Conclusions: This study identified two susceptible gene variants, ZFHX1B rs13382811 and PAX6 rs644242, for anisometropia development in Hong Kong Chinese children, implicating their role in imbalanced refractive change and axial elongation between both eyes.

OCT-based biomarkers for predicting treatment response in eyes with centre-involved diabetic macular oedema treated with anti-VEGF injections: a real-life retina clinic-based study.

BACKGROUND/AIMS: To determine whether a combination of baseline and change in spectral domain-optical coherence tomography (SD-OCT)-based biomarkers can predict visual outcomes in eyes with diabetic macular oedema (DMO) treated with antivascular endothelial growth factors (VEGF) injections. METHODS: This is a retrospective cohort study conducted in Hong Kong, China. 196 eyes with centre-involving DMO, who received anti-VEGF injections between 1 January 2011 and 30 June 2018 were recruited. Medical records of the participants were retrieved retrospectively, visual acuity (VA) at baseline, 6, 12 and 24 months and SD-OCT before initiation and after completion of anti-VEGF treatment were obtained. The SD-OCT images were evaluated for the morphology of DMO, vitreomacular status, presence of disorganisation of retinal inner layers (DRIL), sizes of intraretinal cysts, visibility of external limiting membrane (ELM), ellipsoid zone (EZ) and cone outer segment tip (COST) and the presence of hyper-reflective foci in retina or the choroid. RESULTS: The presence of baseline DRIL, hyper-reflective foci in retina and disruption of ELM/EZ and COST were associated with worse baseline and subsequent VA up to 24 months after treatment. Improvement in DRIL (p=0.048), ELM/EZ (p=0.001) and COST (p=0.002) disruption after treatment was associated with greater improvement in VA at 12 months. Eyes with cystoid macular oedema (p=0.003, OR=8.18) and serous retinal detachment (p=0.011, OR=4.84) morphology were more likely to achieve at least 20% reduction in central subfield thickness. CONCLUSION AND RELEVANCE: Baseline SD-OCT biomarkers and their subsequent change predict VA and improvement in vision in eyes with DMO treated with anti-VEGF injections. We proposed an SD-OCT-based system that can be readily used in real-life eye clinics to improve decision making in the management of DMO.

Relationship between macular intercapillary area measured by optical coherence tomography angiography and central visual field sensitivity in normal tension glaucoma.

PURPOSE: To investigate the relationship of macular intercapillary area (ICA) with macular ganglion cell-inner plexiform layer (GCIPL) thickness and central visual field sensitivity (CVFS) in normal tension glaucoma (NTG). METHODS: Seventy-eight early NTG eyes, 33 moderate-to-severe NTG eyes and 75 normal control eyes were cross-sectional evaluated. All participants underwent swept-source optical coherence tomography angiography (OCT-A; DRI-OCT, Topcon, Tokyo, Japan). A customised MATLAB program was used to quantify macular OCT-A metrics at central 3×3 mm macular region including vascular density (VD), foveal avascular zone (FAZ) area, 10 largest ICA including FAZ area (ICA10_IncFAZ) and excluding FAZ area (ICA10_ExcFAZ). Generalised estimating equation regression models were performed to determine the relationships of OCT-A vascular metrics with GCIPL thickness in the macular region and CVFS. RESULTS: NTG eyes had lower global VD, larger ICA10_IncFAZ, and larger ICA10_ExcFAZ than normal controls (all p≤0.016). In the multivariable analyses, decreased VD (ß=-0.304, p=0.006) and increased ICA (ß=-0.231 for ICA10_IncFAZ and ß=-0.259 for ICA10_ExcFAZ, all p≤0.042) were significantly associated with decreased GCIPL thickness in early NTG eyes but not in moderate-to-severe NTG eyes. ICA enlargement was associated with CVFS in early NTG eyes (ß=-0.310, p=0.009), while VD was associated with CVFS in moderate-to-severe NTG eyes (ß=-0.272, p=0.038). CONCLUSION: ICA enlargement could be a potentially important disease marker of early NTG as reflected by its association with GCIPL thinning and decrease CVFS specifically for early NTG eyes.

Clinically relevant factors associated with a binary outcome of diabetic macular ischaemia: an OCTA study.

AIMS: We investigated the demographic, ocular, diabetes-related and systemic factors associated with a binary outcome of diabetic macular ischaemia (DMI) as assessed by optical coherence tomography angiography (OCTA) evaluation of non-perfusion at the level of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in a cohort of patients with diabetes mellitus (DM). MATERIALS AND METHODS: 617 patients with DM were recruited from July 2015 to December 2020 at the Chinese University of Hong Kong Eye Centre. Image quality assessment (gradable or ungradable for assessing DMI) and DMI evaluation (presence or absence of DMI) were assessed at the level of the SCP and DCP by OCTA. RESULTS: 1107 eyes from 593 subjects were included in the final analysis. 560 (50.59%) eyes had DMI at the level of SCP, and 647 (58.45%) eyes had DMI at the level of DCP. Among eyes without diabetic retinopathy (DR), DMI was observed in 19.40% and 24.13% of eyes at SCP and DCP, respectively. In the multivariable logistic regression models, older age, poorer visual acuity, thinner ganglion cell-inner plexiform layer thickness, worsened DR severity, higher haemoglobin A1c level, lower estimated glomerular filtration rate and higher low-density lipoprotein cholesterol level were associated with SCP-DMI. In addition to the aforementioned factors, presence of diabetic macular oedema and shorter axial length were associated with DCP-DMI. CONCLUSION: We reported a series of associated factors of SCP-DMI and DCP-DMI. The binary outcome of DMI might promote a simplified OCTA-based DMI evaluation before subsequent quantitative analysis for assessing DMI extent and fulfil the urge for an updating diabetic retinal disease staging to be implemented with OCTA.

Light exposure therapy for myopia control: a systematic review and Bayesian network meta-analysis.

AIMS: To compare and rank the myopia control effects of different light wavelengths in children using a systematic review and Bayesian network meta-analysis (Bayesian NMA). METHODS: The review protocol was registered with PROSPERO. We searched PubMed, EMBASE and MEDLINE for relevant clinical and animal studies published as of 2 February 2023. We included studies comparing red, violet or full-spectrum light with controls. Data extracted included descriptive statistics and study outcomes (axial length (AL) elongation and progression of spherical equivalent (SE) refraction). After quality assessment, estimates of treatment effect outcomes (mean differences (MDs) and 95% CIs) were first pooled for the animal and clinical studies in a traditional meta-analysis. To compare and rank the different light wavelengths, the Bayesian NMA was then conducted for all the included clinical studies (12 studies) and separately for only randomised controlled trials (8 studies). MDs, 95% credible intervals (CrIs) and ranks of the various light wavelengths were estimated in the Bayesian NMA. RESULTS: When all clinical studies were included in the Bayesian NMA (12 studies), only red-light significantly slowed AL elongation, MD (95% CrI), -0.38 mm (-0.59 mm to -0.16 mm)/year and SE refraction progression, 0.72D (0.35D to 1.10D)/year compared with controls. It remained the only significant intervention when effect sizes from only RCTs (eight studies) were separately combined, (-0.28 mm (-0.40 mm to -0.15 mm)/year and 0.57D (0.22D to 0.92D)/year, for AL and SE refraction, respectively). CONCLUSION: Myopia control efficacy varied among different wavelengths of light, with red light ranked as the most effective. PROSPERO REGISTRATION NUMBER: Clinical studies: CRD42022368998; animal studies: CRD42022368671.

Association of Ultra-Short-Term Intraocular Pressure Fluctuation With Disease Progression in Primary Angle Closure Glaucoma: The CUPAL Study.

PRCIS: This study demonstrated significant differences in ultra-short-term IOP fluctuations, measured by a contact lens sensor between progressive and stable PACG eyes, during the first one hour after falling asleep. PURPOSE: To identify the most sensitive period for detecting significant ultra-short-term intraocular pressure (IOP) fluctuation associated with disease progression in primary angle closure glaucoma (PACG). MATERIALS AND METHODS: PACG eyes, which had been followed up for over 2 years under the CUHK PACG Longitudinal (CUPAL) Study, were recruited. Eyes with or without functional or structural glaucomatous progression were classified into 'progressive' or 'stable' groups on the basis of serial visual field and retinal nerve fiber layer (RNFL) thickness documentations, respectively. Ultra-short-term IOP fluctuations were recorded by Sensimed Triggerfish sensors (Sensimed AG, Lausanne, Switzerland) with 288 readings over 30 seconds, at 5-minute intervals, over a 24-hour period. In each of 7 activity-related 1-hour periods during the examining day, the mean value of the amplitude-frequency profiles of the signal fluctuations in twelve 30-second intervals was calculated by semivariogram/semi-variance. The 'progressive' and 'stable' groups were compared by permutation tests on functional t-statistics. RESULTS: Among the 25 recruited PACG eyes, 16 eyes were classified as RNFL 'progressive' group (the mean rate of change in global RNFL thickness: -0.199 ±0.128 µm/mo). Higher signal fluctuations, in terms of amplitude-frequency, were found during the first 1-hour period of sleeping in the RNFL 'progressive' group compared with the RNFL 'stable' group ( P =0.028). CONCLUSIONS: Between RNFL 'progressive' and 'stable' PACG eyes, significant differences in ultra-short-term IOP fluctuation at the 1-hour period after falling asleep were identified. The first hour of sleeping may be the most sensitive period for detecting significant ultra-short-term IOP fluctuation in PACG eyes.

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

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; P-trend <0.001). Increased standardized systolic BP was associated with narrower central retinal arteriolar equivalents (ß=-2.276 µm, P<0.001), wider central retinal venular equivalents (1.177, P=0.007), and decreased arteriolar fractal dimensions (ß=-0.004, P=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; P-trend=0.004). Children with both hypertensive BP and either overweightness or obesity had the narrowest central retinal arteriolar equivalents and smallest arteriolar Df (P-trend<0.001 and P-trend=0.007). Conclusions Our findings demonstrate the potential synergistic or additive effects for both hypertensive BP and obesity on retinal vasculature in children.

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

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 (raSatO2 ) and venular oxygen saturation (rvSatO2 ), 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 rvSatO2 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 raSatO2 , rvSatO2 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.

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

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 (rs =-0.602 and -0.925, respectively, both p<0.001), decreased automated FAZ area (rs =-0.344 and -0.766, respectively, both p<0.001), but increased manual FAZ area in both Cirrus 5000 and Triton (rs =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.

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

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)λ=840nm ranges 0.10-0.48 in Cirrus; ODλ=1050nm 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 (rs = -0.576 and -0.922, respectively, both P < 0.001) in Cirrus and Triton, respectively. Although increased OD was significantly correlated with decreased VD in Cirrus (rs = -0.539, P < 0.001), there was no significant correlation between OD with VD in Triton (rs = -0.143, P = 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.

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

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 (ß = 0.687; p = 0.037), shorter axial length (AL) (ß = - 0.171; p = 0.003), thinner subfoveal choroid thickness (ß = - 0.122; p = 0.031), and lower body mass index (BMI) (ß = - 0.090; p = 0.047). Lower VD was associated with more severe DR (ß = - 0.842; p = 0.001), shorter AL (ß = 0.107; p = 0.039), and poorer visual acuity (VA) (ß = - 0.133; p = 0.021). Lower FD was associated with more severe DR (ß = - 0.891; p < 0.001) and with older age (ß = - 0.142; p = 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.

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.

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.

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 (ß=0.110, p<0.001), decreased AL (ß=-0.097, p<0.001) and decreased central macular thickness (ß=-0.008, p<0.001). Decreased vessel density was associated with increased BMI (ß=-4.12×10-4, p=0.006), decreased AL (ß=0.003, p<0.001) and decreased central macular thickness (ß=7.87×10-5, p=0.001). Increased vessel diameter index was associated with female gender (ß=0.020, p=0.007) and decreased AL (ß=-0.020, p<0.001). Decreased fractal dimension was associated with older age (ß=-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.

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

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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.