Is Kidney Function Associated with Age-Related Macular Degeneration?: Findings from the Asian Eye Epidemiology Consortium.

PURPOSE: Chronic kidney disease (CKD) may elevate susceptibility to age-related macular degeneration (AMD) because of shared risk factors, pathogenic mechanisms, and genetic polymorphisms. Given the inconclusive findings in prior studies, we investigated this association using extensive datasets in the Asian Eye Epidemiology Consortium. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-one thousand two hundred fifty-three participants from 10 distinct population-based Asian studies. METHODS: Age-related macular degeneration was defined using the Wisconsin Age-Related Maculopathy Grading System, the International Age-Related Maculopathy Epidemiological Study Group Classification, or the Beckman Clinical Classification. Chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m2. A pooled analysis using individual-level participant data was performed to examine the associations between CKD and eGFR with AMD (early and late), adjusting for age, sex, hypertension, diabetes, body mass index, smoking status, total cholesterol, and study groups. MAIN OUTCOME MEASURES: Odds ratio (OR) of early and late AMD. RESULTS: Among 51 253 participants (mean age, 54.1 ± 14.5 years), 5079 had CKD (9.9%). The prevalence of early AMD was 9.0%, and that of late AMD was 0.71%. After adjusting for confounders, individuals with CKD were associated with higher odds of late AMD (OR, 1.46; 95% confidence interval [CI], 1.11-1.93; P = 0.008). Similarly, poorer kidney function (per 10-unit eGFR decrease) was associated with late AMD (OR, 1.12; 95% CI, 1.05-1.19; P = 0.001). Nevertheless, CKD and eGFR were not associated significantly with early AMD (all P ≥ 0.149). CONCLUSIONS: Pooled analysis from 10 distinct Asian population-based studies revealed that CKD and compromised kidney function are associated significantly with late AMD. This finding further underscores the importance of ocular examinations in patients with CKD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Associations between visual impairment, incident falls and fall frequency among older asians: longitudinal findings from the Singapore Epidemiology of Eye Diseases study.

BACKGROUND: Association between baseline visual impairment (VI) bilaterality and severity, and associated causes; and incident and frequent falls at 6 years in a multiethnic Asian population aged ≥60 years. METHODS: It is a population-based prospective cohort study. Visual acuity was clinically measured at both visits. Self-reported incidence and frequency of falls were defined as having no fall at baseline but having one fall and ≥2 incident falls in the 12 months prior to the follow-up visit, respectively. RESULTS: Of the 1972 older participants (mean age (SD): 67.37 (5.4) years), 253 (12.8%) and 69 (3.5%) reported at least one fall and ≥2 falls, respectively, at a 6-year follow-up. After multivariable adjustments, baseline bilateral VI, but not unilateral, was associated with higher odds of any incident falls (mild bilateral VI: OR=1.79, 95% CI 1.07 to 2.98; moderate-severe VI in one eye and mild VI in the other eye: OR=1.58, 95% CI 1.01 to 2.47). However, having any form of bilateral VI (OR ranging between 2.46 and 4.32; all p<0.05) and even unilateral mild VI (OR=2.34, 95% CI 1.09 to 5.03) significantly increased the odds of incident frequent falls, compared with bilateral normal vision. VI caused by correctable (OR=2.02, 95% CI 1.19 to 3.44) and uncorrectable (OR=3.09, 95% CI 1.08 to 8.80) eye conditions were both associated with greater odds of incident frequent falls, compared with no VI. CONCLUSIONS: Baseline bilateral but not unilateral VI conferred nearly two-fold higher odds of incident fall. Importantly, even mild unilateral VI conferred a substantially greater likelihood of frequent falls from correctable and uncorrectable conditions.

Relationships between Lipid-Related Metabolites and Age-Related Macular Degeneration Vary with Complement Genotype.

Objective: Lipid dysregulation and complement system (CS) activation are 2 important pathophysiology pathways for age-related macular degeneration (AMD). We hypothesized that the relationship between lipids and AMD may also differ according to CS genotype profile. Thus, the objective was to investigate the relationships between lipid-related metabolites and AMD according to CS genotypes. Design: Population-based cross-sectional study. Participants: A total of 6947 participants from Singapore Epidemiology of Eye Diseases study with complete relevant data were included. Methods: We investigated a total of 32 blood lipid-related metabolites from nuclear magnetic resonance metabolomics data including lipoproteins and their subclasses, cholesterols, glycerides, and phospholipids, as well as 4 CS single nucleotide polymorphisms (SNPs): rs10922109 (complement factor H), rs10033900 (complement factor I), rs116503776 (C2-CFB-SKIV2L), and rs2230199 (C3). We first investigated the associations between AMD and the 32 lipid-related metabolites using multivariable logistic regression models. Then, to investigate whether the effect of lipid-related metabolites on AMD differ according to the CS SNPs, we tested the possible interactions between the CS SNPs and the lipid-related metabolites. Main Outcome Measures: Age-related macular degeneration was defined using the Wisconsin grading system. Results: Among the 6947 participants, the prevalence of AMD was 6.1%, and the mean age was 58.3 years. First, higher levels of cholesterol in high-density lipoprotein (HDL) and medium and large HDL particles were associated with an increased risk of AMD, and higher levels of serum total triglycerides (TG) and several very-low-density lipoprotein subclass particles were associated with a decreased risk of AMD. Second, these lipids had significant interaction effects on AMD with 2 CS SNPs: rs2230199 and rs116503776 (after correction for multiple testing). For rs2230199, in individuals without risk allele, higher total cholesterol in HDL2 was associated with an increased AMD risk (odds ratio [OR] per standard deviation increase, 1.20; 95% confidence interval (CI), 1.06-1.37; P = 0.005), whereas, in individuals with at least 1 risk allele, higher levels of these particles were associated with a decreased AMD risk (OR, 0.69; 95% CI, 0.45-1.05; P = 0.079). Conversely, for rs116503776, in individuals without risk allele, higher serum total TG were associated with a decreased AMD risk (OR, 0.84; 95% CI, 0.74-0.95; P = 0.005), whereas, in individuals with 2 risk alleles, higher levels of these particles were associated with an increased risk of AMD (OR, 2.3, 95% CI, 0.99-5.39, P = 0.054). Conclusions: Lipid-related metabolites exhibit opposite directions of effects on AMD according to CS genotypes. This indicates that lipid metabolism and CS may have synergistic interplay in the AMD pathogenesis.

In Vivo Confocal Microscopy in Different Types of Dry Eye and Meibomian Gland Dysfunction.

In vivo confocal microscopy (IVCM) imaging is increasingly popular in ocular surface disease diagnosis and management. We conducted a systematic review to update the use of IVCM in the diagnosis and treatment of dry eye and meibomian gland dysfunction (MGD). A literature review was conducted on IVCM studies in MGD, dry eye disease, systemic disease causing dry eye, dry eye in glaucoma patients, contact lens-associated ocular conditions, graft-versus-host disease, and Sjogren's syndrome-related dry eye. The articles were identified through PubMed and a total number of 63 eligible publications were analyzed in detail. All primary research studies on confocal microscopy on dry eye and related conditions from 2017 onwards were included. The reports were reviewed for their contribution to the existing literature as well as potential biases and drawbacks. Despite limitations such as small field of view, lack of population-based norms, and lack of standardization of image acquisition, interpretation, and quantification, IVCM is useful as a complementary technique for clinical diagnosis in various ocular surface disorders related to dry eye. With advances in hardware and software in the near future, it has the potential for further practical impact.

Three-dimensional modelling of the choroidal angioarchitecture in a multi-ethnic Asian population.

This study aimed to describe the topographic variation of the macula's choroidal angioarchitecture using three-dimensional (3D) choroidal vascularity index (CVI) of healthy eyes from an Asian population and to investigate the associations of CVI. 50 participants were recruited via stratified randomisation based on subfoveal choroidal thickness from the Singapore Epidemiology of Eye Diseases Study. Macular volume scans were acquired using spectral-domain optical coherence tomography with enhanced depth imaging. CVI was assessed based on B-scan binarisation and choroid segmentation. The 3D CVI of the whole, superior, central, and inferior macula were 62.92 ± 1.57%, 62.75 ± 1.93%, 63.35 ± 1.72%, and 62.66 ± 1.70%, respectively, pairwise comparisons P all > 0.05). 3D CVI (Whole Macula) and 2D CVI (Subfoveal) were associated only with each other and not with other ocular and systemic factors. 2D CVI (Subfoveal) had a moderate agreement with 3D CVI (Central Macula) [intraclass corelation coefficient (ICC) = 0.719], and had poorer agreement with 3D CVI of the whole macula, superior, and inferior macula (ICC = 0.591, 0.483, and 0.394, respectively). Scanning volume did not influence 3D CVI measurements. In conclusion, 3D CVI demonstrated no significant topographic variation. CVI was not correlated with demographic or ocular structural features. 2D CVI of the fovea is partially representative of 3D CVI of the macula.

Retinal microvascular signs in COVID-19.

BACKGROUND/AIMS: To explore if retinal findings are associated with COVID-19 infection. METHODS: In this prospective cross-sectional study, we recruited participants positive for COVID-19 by nasopharyngeal swab, with no medical history. Subjects underwent retinal imaging with an automated imaging device (3D OCT-1 Maestro, Topcon, Tokyo, Japan) to obtain colour fundus photographs (CFP) and optical coherence tomographic (OCT) scans of the macula. Data on personal biodata, medical history and vital signs were collected from electronic medical records. RESULTS: 108 patients were recruited. Mean age was 36.0±5.4 years. 41 (38.0%) had symptoms of acute respiratory infection (ARI) at presentation. Of 216 eyes, 25 (11.6%) had retinal signs-eight (3.7%) with microhaemorrhages, six (2.8%) with retinal vascular tortuosity and two (0.93%) with cotton wool spots (CWS). 11 eyes (5.1%) had hyper-reflective plaques in the ganglion cell-inner plexiform layer layer on OCT, of which two also had retinal signs visible on CFP (CWS and microhaemorrhage, respectively). There was no significant difference in the prevalence of retinal signs in symptomatic versus asymptomatic patients (12 (15.0%) vs 13 (9.6%), p=0.227). Patients with retinal signs were significantly more likely to have transiently elevated blood pressure than those without (p=0.03). CONCLUSION: One in nine had retinal microvascular signs on ocular imaging. These signs were observed even in asymptomatic patients with normal vital signs. These retinal microvascular signs may be related to underlying cardiovascular and thrombotic alternations associated with COVID-19 infection.

Developing a normative database for retinal perfusion using optical coherence tomography angiography.

Visualizing and characterizing microvascular abnormalities with optical coherence tomography angiography (OCTA) has deepened our understanding of ocular diseases, such as glaucoma, diabetic retinopathy, and age-related macular degeneration. Two types of microvascular defects can be detected by OCTA: focal decrease because of localized absence and collapse of retinal capillaries, which is referred to as the non-perfusion area in OCTA, and diffuse perfusion decrease usually detected by comparing with healthy case-control groups. Wider OCTA allows for insights into peripheral retinal vascularity, but the heterogeneous perfusion distribution from the macula, parapapillary area to periphery hurdles the quantitative assessment. A normative database for OCTA could estimate how much individual's data deviate from the normal range, and where the deviations locate. Here, we acquired OCTA images using a swept-source OCT system and a 12×12 mm protocol in healthy subjects. We automatically segmented the large blood vessels with U-Net, corrected for anatomical factors such as the relative position of fovea and disc, and segmented the capillaries by a moving window scheme. A total of 195 eyes were included and divided into 4 age groups: < 30 (n=24) years old, 30-49 (n=28) years old, 50-69 (n=109) years old and >69 (n=34) years old. This provides an age-dependent normative database for characterizing retinal perfusion abnormalities in 12×12 mm OCTA images. The usefulness of the normative database was tested on two pathological groups: one with diabetic retinopathy; the other with glaucoma.

Fructus lycii: A Natural Dietary Supplement for Amelioration of Retinal Diseases.

Fructus lycii (F. lycii) is an exotic "berry-type" fruit of the plant Lycium barbarum that is characterized by a complex mixture of bioactive compounds distinguished by their high antioxidant potential. F. lycii is used in traditional Chinese home cooking and in the Chinese Pharmacopeia as an aid to vision and longevity as well as a remedy for diabetes to balance "yin" and "yang" in the body for about two centuries. Although a myriad of bioactive compounds have been isolated from F. lycii, polysaccharides, carotenoids, flavonoids, and phenolics represent the key functional components of F. lycii. F. lycii has been shown to exhibit a wide range of biological activities in experimental settings including antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects. Despite its medicinal role dating back to the eighteenth century in the Far East and robust evidence of beneficial effects on ocular health and retinal diseases originating mainly from studies in animal models, the role of F. lycii in the clinical management of retinal diseases is yet to be established. This article comprehensively reviews the literature germane to F. lycii and retinal diseases with particular emphasis on age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa, which are commonly seen in clinical practice.

Approaches to quantify optical coherence tomography angiography metrics.

Optical coherence tomography (OCT) has revolutionized the field of ophthalmology in the last three decades. As an OCT extension, OCT angiography (OCTA) utilizes a fast OCT system to detect motion contrast in ocular tissue and provides a three-dimensional representation of the ocular vasculature in a non-invasive, dye-free manner. The first OCT machine equipped with OCTA function was approved by U.S. Food and Drug Administration in 2016 and now it is widely applied in clinics. To date, numerous methods have been developed to aid OCTA interpretation and quantification. In this review, we focused on the workflow of OCTA-based interpretation, beginning from the generation of the OCTA images using signal decorrelation, which we divided into intensity-based, phase-based and phasor-based methods. We further discussed methods used to address image artifacts that are commonly observed in clinical settings, to the algorithms for image enhancement, binarization, and OCTA metrics extraction. We believe a better grasp of these technical aspects of OCTA will enhance the understanding of the technology and its potential application in disease diagnosis and management. Moreover, future studies will also explore the use of ocular OCTA as a window to link ocular vasculature to the function of other organs such as the kidney and brain.

Optical Coherence Tomography Angiography in Diabetes and Diabetic Retinopathy.

Diabetic retinopathy (DR) is a common complication of diabetes mellitus that disrupts the retinal microvasculature and is a leading cause of vision loss globally. Recently, optical coherence tomography angiography (OCTA) has been developed to image the retinal microvasculature, by generating 3-dimensional images based on the motion contrast of circulating blood cells. OCTA offers numerous benefits over traditional fluorescein angiography in visualizing the retinal vasculature in that it is non-invasive and safer; while its depth-resolved ability makes it possible to visualize the finer capillaries of the retinal capillary plexuses and choriocapillaris. High-quality OCTA images have also enabled the visualization of features associated with DR, including microaneurysms and neovascularization and the quantification of alterations in retinal capillary and choriocapillaris, thereby suggesting a promising role for OCTA as an objective technology for accurate DR classification. Of interest is the potential of OCTA to examine the effect of DR on individual retinal layers, and to detect DR even before it is clinically detectable on fundus examination. We will focus the review on the clinical applicability of OCTA derived quantitative metrics that appear to be clinically relevant to the diagnosis, classification, and management of patients with diabetes or DR. Future studies with longitudinal design of multiethnic multicenter populations, as well as the inclusion of pertinent systemic information that may affect vascular changes, will improve our understanding on the benefit of OCTA biomarkers in the detection and progression of DR.

Optical coherence tomography angiography for the assessment of choroidal vasculature in high myopia.

AIMS: To assess specific layers of the choroid in highly myopic young adults and to examine their associations with levels of myopia. METHODS: We recruited 51 young myopes (n=91 eyes) from the Singapore Cohort of Risk Factors for Myopia cohort. We performed standardised optical coherence tomography (OCT) and OCT angiography imaging and developed a novel segmentation technique assessing choroidal layers' thickness (overall choroidal thickness (CT), medium-vessel choroidal layer (MVCL) thickness, large-vessel choroidal layer (LVCL)) and vasculature (choroidal vessel density (%), choroidal branch area (CBA, %) and mean choroidal vessel width (MCVW, mm)). RESULTS: We found that eyes with extreme myopia (EM) had thinner vascular layers compared with high myopia (HM), that is, LVCL (36.0±1.5 vs 39.2±1.2 µm, p=0.002) and MVCL (185.5±5.7 vs 198.2±4.6 µm, p=0.014). Overall CT was thinnest in the nasal and inferior quadrants in EM (nasal: 157.1±9.6 vs 187.2±8.3 µm, p<0.001; superior: 236.6±11.1 vs 257.0±9.5 µm, p=0.02; temporal: 228.0±10.6 vs 254.3±8.8 µm, p=0.012; and inferior quadrant: 198.7±10.0 vs 239.8±8.3 µm, p=<0.001) when compared with HM. We also observed significantly more vessel branching in eyes with EM as compared with eyes with HM (CBA, 10.2%±0.7% vs 9.95%±0.8%, p=0.018). CONCLUSIONS: The novel segmentation technique and introduced choroidal parameters may serve as new biomarkers to study disease conditions in myopia.

Association between antenatal blood pressure and 5-year postpartum retinal arteriolar structural and functional changes.

OBJECTIVE: Studies have shown that hypertensive disorders of pregnancy (HDP) are associated with both postpartum retinal microvascular changes and cardiovascular (CV) risks. However, the underlying mechanism of HDP transitioning to microvascular and macrovascular changes remains unknown, due to the interaction between microvasculature and CV risks. In this study, we examined whether associations between antenatal systolic blood pressure (SBP) and postpartum retinal arteriolar changes are independent of postpartum CV risks. METHODS: We included 276 Singaporean mothers attending both baseline index pregnancy (2009-2010) and 5-year postpartum follow-up visits (2014-2015). We measured SBP at baseline. At follow-up, we assessed retinal microvascular structure and function with retinal photography and dynamic vessel analyser, together with CV risks using a validated 2008 Framingham Risk Score (FRS). We performed a traditional four-step mediation analysis using linear regression by adjusting for a series of baseline characteristics: age, ethnicity, college degree, prepregnancy body mass index and gestational diabetes mellitus diagnosis at baseline. RESULTS: We found that each 10 mm Hg increase in baseline SBP was associated with reduced arteriolar calibre (-1.3 µm; 95% CI -3.0 to 0.2) and fractal dimension (-0.4 degrees of freedom (df); -1.0 to 0.2), and significantly with increased arteriolar constriction (0.5%; 0.001 to 1.0) at 5-year postpartum. Even though baseline SBP was associated with postpartum FRS, the latter was not associated with any retinal arteriolar measures. Therefore, no further mediation analysis was required. CONCLUSION: Our study suggested that elevated SBP during pregnancy was associated with suboptimal retinal arteriolar structure and function independent of postpartum CV risks.